Variant IgG FC Polypeptides and Uses Thereof

Abstract

Embodiments provided herein provide variant IgG Fc polypeptides, dimeric molecules, pharmaceutical compositions, and methods that can be used to target cells and modulate their activity to treat disorders such as autoimmune disorders or cancer.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 380,842, filed October 25, 2022, U.S. Provisional Application No. 63 / 380,853, filed October 25, 2022, U.S. Provisional Application No. 63 / 493,356, filed March 31, 2023, and U.S. Provisional Application No. 63 / 517,493, filed August 3, 2023, each of which is incorporated by reference herein in its entirety.

[0002] Reference to an electronically submitted sequence listing This application contains a Sequence Listing that has been submitted electronically in XML file format, which is incorporated herein by reference in its entirety. The XML copy, created on October 25, 2023, is named "SES-005WO_SEQ.XML" and is 132,581 bytes in size.

[0003] Embodiments provided herein relate to compositions that target cells to regulate immune responses. [Background technology]

[0004] FcγRIIβ is the only FcγR expressed on B cells (Smith, KGC, and Clatworthy, MR, Nat Rev Immunol. 2010 May;10(5):328-343). It has been reported that the interaction of antibody Fc regions with FcγRIIβ suppresses the primary immune response of B cells (Smith, KGC, and Clatworthy, MR, Nat Rev Immunol. 2010 May;10(5):328-343). Furthermore, it has been reported that cross-linking of FcγRIIβ on B cells with the B cell receptor (BCR) via immune complexes in the blood suppresses B cell activation and antibody production by B cells. IgG1, the predominantly used commercially available therapeutic antibody, is known to bind not only to FcγRIIβ but also strongly to activating FcγRs. By utilizing an Fc region with enhanced FcγRIIβ binding or improved FcγRIIβ binding selectivity relative to activating FcγRs, it may be possible to develop therapeutic antibodies with greater immunosuppressive properties than those of IgG1. Thus, antibodies having an Fc with improved FcγRIIβ binding activity have been suggested to be promising therapeutic agents for inflammatory diseases, such as autoimmune diseases. The embodiments provided herein meet these and other needs. Summary of the Invention

[0005] In some embodiments, the variant IgG Fc polypeptide selectively binds to FcγRIIβ over FcγRIIα, wherein the variant IgG Fc polypeptide is selected from the group consisting of VFC-1, VFC-2, VFC-3, VFC-4, VFC-5, VFC-6, VFC-7, VFC-8, VFC-9, VFC-10, VFC-11, VFC-12, VFC-13, VFC-14, VFC-15, VFC-16, VFC-17, VFC-18, VFC-19, VFC-20, VFC-21, VFC-22, VFC-23, VFC-24, VFC-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC-37, VFC-38, VFC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC-48, VFC-49, VFC-50, VFC-51, VFC-52, VFC-53, VFC-54, VFC-55, VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC-61, VFC-62, VFC-63, VFC-64, VFC-65, VFC-66, VFC-67, VFC-68, VFC-69, VFC-70, VFC-71, VFC-72, VFC-73, VFC-74, VFC-75, VFC-76, VFC-77, VFC-78, VFC-79, V 4, VFC-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC- 36, VFC-37, VFC-38, VFC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC- 48, VFC-49, VFC-50, VFC-51, VFC-52, VFC-53, VFC-54, VFC-55, VFC-56, VFC-57, VFC-58, VFC-59, VFC -60, VFC-61, VFC-62, VFC-63, VFC-64, VFC-65, VFC-66, VFC-67, VFC-68, VFC-69, VFC-70, VFC-71, VFC In some embodiments, a variant IgG Fc polypeptide is provided, comprising a mutation selected from a mutation associated with any of VFC-72, VFC-73, VFC-74, VFC-75, VFC-76, VFC-77, VFC-78, VFC-79, VFC-80, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, VFC-87, VFC-88, VFC-89, or VFC-90.

[0006] In some embodiments, the variant IgG Fc polypeptide selectively binds to FcγRIIβ over FcγRIIα, wherein the variant IgG Fc polypeptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, 52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO:104; and a variant IgG Fc polypeptide; and an inhibitory receptor effector domain.

[0007] In some embodiments, the variant IgG Fc polypeptide selectively binds to FcγRIIβ over FcγRIIα, wherein the variant IgG Fc polypeptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, 52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO:104. Polypeptides are provided that include an Fc polypeptide, an inhibitory receptor effector domain, and an FcγRII-binding effector domain.

[0008] In some embodiments, a method of treating an autoimmune disorder in a subject is provided, the method comprising administering to the subject a variant IgG Fc polypeptide such as those provided herein, a polypeptide such as those provided herein, or a pharmaceutical composition comprising same.

[0009] In some embodiments, a method of treating cancer in a subject is provided, the method comprising administering to the subject a variant IgG Fc polypeptide such as those provided herein, a polypeptide such as those provided herein, or a pharmaceutical composition comprising same.

[0010] In some embodiments, methods are provided for modulating the interaction of at least two distinct types of cells, the methods comprising administering to a subject a variant IgG Fc polypeptide such as those provided herein, a polypeptide such as those provided herein, or a pharmaceutical composition comprising same.

[0011] In some embodiments, methods are provided for inhibiting activated immune cells in contact with B cells, antigen-presenting cells (APCs), or myeloid cells, the methods comprising administering to a subject a variant IgG Fc polypeptide such as those provided herein, a polypeptide such as those provided herein, or a pharmaceutical composition comprising same.

[0012] In some embodiments, methods are provided for activating or enhancing the behavior of activated immune cells in contact with B cells, antigen-presenting cells (APCs), or myeloid cells, the methods comprising administering to a subject a variant IgG Fc polypeptide such as those provided herein, a polypeptide such as those provided herein, or a pharmaceutical composition comprising same. [Brief explanation of the drawings]

[0013] [Figure 1A] 1 is a bar graph showing IL-2 production levels after treatment with VFC-IR agonists or control molecules. [Figure 1B]1 is a bar graph showing IFNg production levels after treatment with VFC-IR agonists or control molecules. [Figure 1C] 1 is a bar graph showing TNFα production levels after treatment with VFC-IR agonists or control molecules. [Figure 2A] 1 illustrates the binding affinities of various articles. [Figure 2B] 1 illustrates the binding affinities of various articles. [Figure 2C] 1 illustrates the binding affinities of various articles. [Figure 3] 1 illustrates TNF-alpha production in response to various compounds. [Figure 4] Illustrates granzyme B and IFN-gamma production in response to various compounds. [Figure 5A] Illustrates ADCC induction in response to various compounds. [Figure 5B] Illustrates ADCC induction in response to various compounds. [Figure 6] Illustrates C1q binding to various articles. DETAILED DESCRIPTION OF THE INVENTION

[0014] This application incorporates by reference U.S. Provisional Application No. 63 / 380,842, filed October 25, 2022, U.S. Provisional Application No. 63 / 380,853, filed October 25, 2022, U.S. Provisional Application No. 63 / 493,356, filed March 31, 2023, and U.S. Provisional Application No. 63 / 517,493, filed August 3, 2023, each of which is incorporated by reference herein in its entirety.

[0015] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0016] As used herein, the term "about" means that a numerical value is approximate and that small variations do not significantly affect the practice of the disclosed embodiments. When a numerical limit is used, unless otherwise indicated by context, "about" means that the numerical value can vary by ±5% and remain within the range of the disclosed embodiments. Thus, about 100 means 95 to 105.

[0017] As used herein, the term "animal" includes, but is not limited to, humans and non-human vertebrates, such as wild, domestic, and farm animals. As used herein, the term "mammal" means a rodent (i.e., mouse, rat, or guinea pig), monkey, cat, dog, cow, horse, pig, or human. In some embodiments, the mammal is a human.

[0018] As used herein, the term "contacting" refers to bringing two elements together in an in vitro system or in an in vivo system. For example, "contacting" a therapeutic compound with an individual or patient or cell includes administering the compound to an individual or patient, such as a human, and introducing the compound into a sample containing, for example, a cell or purified preparation containing the target.

[0019] As used herein, the terms "comprising" (and any form of comprising, e.g., "comprise," "comprises," and "comprised"), "having" (and any form of having, e.g., "have" and "has"), "including" (and any form of including, e.g., "includes" and "include"), or "containing" (and any form of containing, e.g., "contains" and "contain") are inclusive or open-ended and do not exclude additional, unrecited, elements or method steps. Any composition or method reciting the term "comprising" should be understood to also describe a composition that consists of, consists of, or consists essentially of the recited components or elements.

[0020] As used herein, the terms "fused" or "linked," when used in reference to proteins or molecules having different domains or heterologous sequences, mean that the protein domains are part of the same peptide chain, connected to each other either by peptide bonds or other covalent bonds. The domains or segments can be directly linked or fused to each other, or another domain or peptide sequence can be between the two domains or sequences, and such sequences would still be considered fused or linked to each other.

[0021] As used herein, the terms "individual," "subject," or "patient," used interchangeably, refer to any animal, including a mammal, e.g., a mouse, rat, other rodent, rabbit, dog, cat, pig, cow, sheep, horse, or primate, such as a human.

[0022] As used herein, the term "inhibit" refers to a result, symptom, or activity that is reduced compared to the activity or result in the absence of the compound inhibiting the result, symptom, or activity. In some embodiments, the result, symptom, or activity is inhibited by about or at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99%. A result, symptom, or activity can also be inhibited if it is completely eliminated or abolished.

[0023] As used herein, the phrase "in need of" means that a subject has been identified as having a need for a particular method or treatment. In some embodiments, identification can be by any means of diagnosis. A subject may be in need of any of the methods and treatments described herein. In some embodiments, the subject is in or moves to an environment where a particular disease, disorder, or condition is prevalent.

[0024] As used herein, the phrase "an integer from X to Y" means any integer, inclusive. For example, the phrase "an integer from 1 to 5" means 1, 2, 3, 4, or 5.

[0025] As used herein, the phrase "ophthalmically acceptable" means having no lasting adverse effects on the treated eye or its function, or on the general health of the treated subject. However, it is recognized that transient effects, such as mild irritation or a "stinging" sensation, are common with topical ophthalmic administration of drugs, and the presence of such transient effects is not inconsistent with the composition, formulation, or ingredients (e.g., excipients) in question being "ophthalmically acceptable," as defined herein. In some embodiments, a pharmaceutical composition may be ophthalmically acceptable or suitable for ophthalmic administration.

[0026] In some embodiments, the term "therapeutic molecule" can be used interchangeably with "therapeutic compound," "molecule," or "therapeutic agent," and refers to any polypeptide or protein described herein.

[0027] "Specific binding" or "specifically binds to" or "specific for" a particular antigen, target, or epitope means binding that is measurably different from non-specific interactions. Specific binding can be measured, for example, by determining the binding of a molecule compared to the binding of a control molecule, which is generally a molecule of similar structure that does not have binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target.

[0028] Specific binding to a particular antigen, target, or epitope is, for example, at least about 10 -4M , at least about 10 -5M , at least about 10 -6M , at least about 10 -7M , at least about 10 -8M , at least about 10 -9M , alternatively at least about 10 -10M , at least about 10 -11M , at least about 10 -12M , or K exceeding it D where K D refers to the off-rate of a particular antibody-target interaction. Typically, an antibody that specifically binds to an antigen or target has a K that is 2-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, 500-fold, 1000-fold, 5,000-fold, 10,000-fold, or more greater than a control molecule, or at least 2-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, 500-fold, 1000-fold, 5,000-fold, 10,000-fold, or more greater than a control molecule, compared to the antigen or epitope. D It has.

[0029] In some embodiments, specific binding to a particular antigen, target, or epitope is, for example, a K for the target, antigen, or epitope that is at least 2-fold, 4-fold, 5-fold, 20-fold, 50-fold, 100-fold, 500-fold, 1000-fold, 5,000-fold, 10,000-fold, or more, greater than a control. Aor K a where K A or K a refers to the association rate of a particular antibody-antigen interaction.

[0030] As provided herein, the compounds and compositions provided herein can be used in the therapeutic methods provided herein. As used herein, the terms "treat," "treated," or "treating" refer to both therapeutic treatments and prophylactic measures, the purpose of which is to slow (alleviate) an undesirable physiological condition, disorder, or disease, or to obtain a beneficial or desired clinical result. For purposes of these embodiments, a beneficial or desired clinical result includes, but is not limited to, alleviation of symptoms; reduction in the severity of a condition, disorder, or disease; stabilization (i.e., not worsening) of the condition, disorder, or disease state; delay in onset or slowing of the condition, disorder, or disease progression; improvement or remission (whether partial or total) of the condition, disorder, or disease state, whether detectable or undetectable; improvement in at least one measurable physical parameter, not necessarily discernible by the patient; or enhancement or amelioration of the condition, disorder, or disease. Treatment includes eliciting a clinically significant response without excessive levels of side effects. Treatment, where applicable to a particular disease, also includes prolonging survival compared to expected survival if not receiving treatment. Thus, "treatment of an autoimmune condition" or "treating autoimmunity" refers to the activity of alleviating or ameliorating any of the primary phenomena or secondary symptoms associated with the autoimmune conditions described herein, as well as other conditions, when the terms "treat," "treated," or "treating" are used in conjunction with such conditions.

[0031] As used herein, the terms "variant," "molecule," "therapeutic agent," "therapeutic compound," "compound," "polypeptide," or "protein" can be used interchangeably and refer to the variants, molecules, therapeutic agents, therapeutic compounds, compounds, polypeptides, and proteins disclosed herein.

[0032] Variant Fc molecules As used herein, "isotype" refers to the immunoglobulin class (e.g., IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgD, and IgE antibodies) encoded by heavy chain constant domain genes. The full-length amino acid sequence of each wild-type human IgG constant region (including all domains, i.e., CH1 domain, hinge, CH2 domain, and CH3 domain) is cataloged in the UniProt database available online, for example, as P01857 (IgG1), P01859 (IgG2), P01860 (IgG3), and P01861 (IgG4), or their different allotypes (SEQ ID NOs: 1, 2, 3, and 4, respectively). As used herein, a domain of a heavy chain constant region, e.g., a hinge, is of the "IgG1 isotype," "IgG2 isotype," "IgG3 isotype," or "IgG4 isotype" if the domain comprises the amino acid sequence of the corresponding domain of each isotype or a variant thereof (which has higher homology to the corresponding domain of each isotype than to that of other isotypes).

[0033] As used herein, "variant Fc polypeptide" and "variant IgG Fc polypeptide" refer to the same Fc polypeptide that contains at least one mutation compared to the wild-type isotype amino acid sequence; therefore, the terms "variant Fc polypeptide" and "variant IgG Fc polypeptide" can be used interchangeably.

[0034] "Allotype" refers to naturally occurring variants within a particular isotype group, which variants differ in some amino acids (see, e.g., Jefferies et al. (2009) mAbs 1:1). The molecules described herein can be of any allotype.

[0035] A "wild-type" protein or portion thereof is a version of a protein found in nature. The amino acid sequence of a wild-type protein, e.g., a heavy chain constant region, is the amino acid sequence of a naturally occurring protein. Due to allotypic differences, there may be more than one amino acid sequence for a wild-type protein. For example, there are several allotypes of the naturally occurring human IGg1 heavy chain constant region (e.g., Jeffries et al. (2009) mAbs 1:1).

[0036] Immunoglobulins can be from any of the commonly known isotypes, including, but not limited to, IgA, secretory IgA, IgG, and IgM. The IgG isotype is divided into subclasses in certain species: IgG1, IgG2, IgG3, and IgG4 in humans, and IgG1, IgG2a, IgG2b, and IgG3 in mice. In certain embodiments, the antibodies described herein are of the human IgG1 or IgG2 subtype. Immunoglobulins, such as human IgG1, exist in several allotypes that differ from each other in at most a few amino acids.

[0037] In some embodiments, the IgG protein (hinge region underlined) is as provided in Table 1. [Table 1]

[0038] "Fc region" (Fragment Crystallizable Region) or "Fc domain" or "Fc" refers to the C-terminal region of an antibody heavy chain that mediates binding of immunoglobulins to host tissues or factors, including binding to Fc receptors located on various cells of the immune system (e.g., effector cells) or binding to the first component (C1q) of the classical complement system. Thus, the Fc region of an antibody of isotype IgG comprises the heavy chain constant region of the antibody excluding the first constant region immunoglobulin domain (CH1). In IgG, IgA, and IgD antibody isotypes, the Fc region comprises CH2 and CH3 constant domains in each of the antibody's two heavy chains, while IgM and IgE Fc regions comprise three heavy chain constant domains (CH domains 2-4) in each polypeptide chain. In the case of IgG, the Fc region comprises immunoglobulin domains consisting of the hinge, CH2, and CH3. For purposes herein, the Fc region is defined as beginning at amino acid 216 and ending at amino acid 447, with numbering according to the EU index as in Kabat, Kabat et al. (1991) Sequences of Proteins of Immunological Interest, National Institutes of Health, Bethesda, MD, and according to Figures 3c-3f of U.S. Patent Application Publication No. 2008 / 0248028, which may be referred to as EU numbering. In some embodiments, the Fc region includes a hinge region. The Fc can be a native (or naturally occurring or wild-type) Fc, including any allotypic variants, or a variant Fc (e.g., a non-naturally occurring Fc), including, for example, 1, 2, 3, 4, 5, 1-5, 1-10, or 5-10 or more amino acid mutations, e.g., substitutions, additions, or deletions. For example, a variant Fc may comprise an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a wild-type Fc. The modified or mutated Fc may have enhanced or reduced effector function and / or half-life.Fc can refer to this region in isolation or in the context of a protein polypeptide comprising Fc, such as an "Fc region-containing binding protein" (e.g., an antibody or immunoadhesin), also referred to as an "Fc fusion protein." In some embodiments, the modified or variant Fc molecule has enhanced binding to FcγRIIb.

[0039] The terms "hinge," "hinge domain," or "hinge region," or "antibody hinge region" refer to the domain of the heavy chain constant region that connects the CH1 domain to the CH2 domain and includes the upper, middle, and lower portions of the hinge (Roux et al. J. Immunol. 1998 161:4083). The hinge provides varying levels of flexibility between the binding and effector regions of an antibody and also provides a site for intermolecular disulfide bonding between the two heavy chain constant regions. The term "hinge" includes wild-type hinges and variants thereof (e.g., non-naturally occurring hinges or modified hinges). For example, the term "IgG1 hinge" includes the wild-type IgG1 hinge shown below, as well as variants having 1, 2, 3, 4, 5, 1-3, 1-5, 3-5, and / or up to 5, 4, 3, 2, or 1 mutations, e.g., substitutions, deletions, or additions. In some embodiments, the hinge region is as provided in Table 2. [Table 2]

[0040] The term "CH1 domain" refers to the heavy chain constant region that connects the variable domain to the hinge within the heavy chain constant domain. As used herein, CH1 domain includes wild-type CH1 domains and variants thereof (e.g., non-naturally occurring CH1 domains or modified CH1 domains). As used herein, CH1 domains include amino acid residues 1-98 of IgG1, 1-98 of IgG2, 1-98 of IgG3, and 1-98 of IgG4. For example, the term "CH1 domain" includes wild-type CH1 domains and variants thereof with 1, 2, 3, 4, 5, 1-3, 1-5, 3-5, and / or up to 5, 4, 3, 2, or 1 mutations, e.g., substitutions, deletions, or additions.

[0041] The term "CH2 domain" refers to the heavy chain constant region that connects the hinge to the CH3 domain in the heavy chain constant domain. As used herein, CH2 domains include wild-type CH2 domains and variants thereof (e.g., non-naturally occurring CH2 domains or modified CH2 domains). As used herein, CH2 domains include amino acid residues 111-223 of IgG1, 111-219 of IgG2, 161-270 of IgG3, and 111-220 of IgG4. For example, the term "CH2 domain" includes wild-type CH2 domains and variants thereof with 1, 2, 3, 4, 5, 1-3, 1-5, 3-5, and / or up to 5, 4, 3, 2, or 1 mutations, e.g., substitutions, deletions, or additions.

[0042] The term "CH3 domain" refers to a heavy chain constant region C-terminal to the CH2 domain within a heavy chain constant domain. As used herein, CH3 domains include wild-type CH3 domains and variants thereof (e.g., non-naturally occurring CH3 domains or modified CH3 domains). As used herein, CH3 domains include amino acid residues 224-330 of IgG1, 220-326 of IgG2, 271-376 of IgG3, and 226-322 of IgG4. For example, the term "CH3 domain" includes wild-type CH3 domains and variants thereof with 1, 2, 3, 4, 5, 1-3, 1-5, 3-5, and / or up to 5, 4, 3, 2, or 1 mutations, e.g., substitutions, deletions, or additions.

[0043] In some embodiments, the hinge / CH2 domain has an amino acid sequence such as those provided in Table 3 below. [Table 3]

[0044] Without being bound by any particular theory, mutation or isotype swapping of the entire hinge or CH2 region of an IgG1, or certain portions of the hinge or CH2 region, results in a modified IgG1 with enhanced or altered properties compared to an IgG1 with a wild-type IgG1 constant region. For example, an IgG1 can have residues 111-223 replaced with residues 111-220 of IgG4. Other non-limiting examples include IgG1s with at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% of residues 111-223 replaced with at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% of residues 111-220 of IgG4.

[0045] In some embodiments, the variant Fc molecule is a hybrid Fc molecule comprising sequences from at least two IgG isotypes. For example, the variant Fc molecule may comprise a CH2 or CH3 region from one or more other isotypes. For example, the variant Fc may be an IgG1 / IgG4 Fc molecule.

[0046] In some embodiments, the variant Fc comprises a CH2 region swapped from another IgG isotype. Examples of CH2 regions include: SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA (IgG1 CH2, SEQ ID NO: 100), or Examples of IgG4 antibodies include, but are not limited to, SVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKA (IgG4 CH2, SEQ ID NO: 101).

[0047] Provided herein are variant Fc molecules comprising variant Fc domains. Exemplary variant Fc molecules comprising variant Fc domains comprise an IgG1 hinge, CH1 domain, CH2 domain, and CH3 domain, in which at least one amino acid residue is mutated, the mutation being a substitution, insertion, or deletion. In some embodiments, the insertion may be 1 to 5 residues. In some embodiments, the variant Fc molecule comprises an IgG1 hinge and an IgG4 CH2 domain. In some embodiments, the variant Fc molecule comprises a mutated variant IgG1 hinge and an IgG4 CH2 domain. The variant Fc molecule may have effector function similar to that of wild-type IgG or may be engineered to have enhanced effector function compared to that of wild-type IgG. In some embodiments, the variant Fc molecule may have FcγRIIβ binding affinity similar to that of wild-type IgG. In some embodiments, the variant Fc molecule may have FcγRIIβ binding affinity that is enhanced to that of wild-type IgG. The variant Fc molecule may comprise a wild-type CH1, hinge, CH2, and / or CH3 domain, or a variant thereof, e.g., a CH1, hinge, CH2, and / or CH3 domain having one or more amino acid substitutions, deletions, or additions compared to the corresponding wild-type domain, and / or having an amino acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical, or more, to the corresponding wild-type sequence.

[0048] In some embodiments, the variant Fc molecule comprises mutations that confer selective binding to FcγRIIβ over FcγRIIα. As used herein, with respect to FcγRIIβ, the term "selective binding" means that the Fc domain binds preferentially to FcγRIIβ over FcγRIIα, i.e., with higher affinity to FcγRIIβ than to FcγRIIα. Examples of such mutations are provided, for example, in US7662926, US7655229, US2009 / 0087428, US10919952, US2007 / 0253948, and US2006 / 0073142, each of which is incorporated by reference in its entirety, including the specific mutations described that affect FcγRIIβ binding. In some embodiments, the mutations are as described in Shields et al., J. Biol. Chem. 2001, 276:6591-6604, which is incorporated herein by reference in its entirety.

[0049] In some embodiments, the Fc mutations are those disclosed in U.S. Patent No. 10,618,965; EP Serial No. 2679681; EP Serial No. 3604330, US 2014 / 0093496, US 2015 / 0203577, U.S. Patent No. 9,540,451, EP Serial No. 2331578; EP Serial No. 3190128; U.S. Patent No. 9,902,773; EP Serial No. 3342782, U.S. Publication No. 2020 / 0332024; EP Serial No. 2796469; EP Serial No. 2331578; EP Serial No. 3190128; U.S. Patent No. 9,902,773, EP Serial No. 2331578; EP Serial No. No. 3190128, U.S. Patent No. 9,493,578, U.S. Patent No. 9,394,366, U.S. Patent No. 9,914,778, EP Serial No. 2940043, US 9,890,218, EP Serial No. 2940135; U.S. Patent No. 10,766,960, U.S. Patent No. 10,919,953, EP 3721900, EP 2889377, US 2016 / 0039912, EP 2982689, or EP 3783017, each of which is incorporated by reference in its entirety, including the described specific mutations that affect FcγRIIb or FcγRIIa binding.

[0050] In some embodiments, the Fc polypeptide comprises a mutation, mutations, or set of mutations that increase selectivity for FcγRIIb. In some embodiments, the Fc polypeptide comprises a mutation, mutation, or set of mutations that increase affinity for FcγRIIb. In some embodiments, the Fc polypeptide comprises a mutation, mutation, or set of mutations that increase selectivity and affinity for FcγRIIb. In some embodiments, the Fc polypeptide comprises a mutation, mutation, or set of mutations that increase selectivity for FcγRIIb over FcγRIIa. In some embodiments, the Fc polypeptide comprises a mutation, mutation, or set of mutations that increase affinity for FcγRIIb over FcγRIIa. In some embodiments, the Fc polypeptide comprises a mutation, mutation, or set of mutations that increase selectivity and affinity for FcγRIIb over FcγRIIa. In some embodiments, the mutation, mutation, or set of mutations is such as those described herein.

[0051] In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 226 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 227 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 229 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 230 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 231 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 232 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 233 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 234 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 235 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 236 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 237 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 238 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228, 234, 235, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution.In some embodiments, the variant Fc domain comprises mutations corresponding to the mutations at positions 228 and 234 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to the mutations at positions 228 and 235 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to the mutations at positions 234 and 235 according to SEQ ID NO: 88.

[0052] In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at positions 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 268, 274, 276, 296, 300, 309, 327, 330, 331, 339, or any combination thereof, according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228, 234, 235, 268, 274, 276, 296, 300, 309, 327, 330, 331, 339, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228, 234, 235, 268, 274, 296, 327, 330, 331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228, 268, 274, 296, 327, 330, 331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228, 234, 268, 274, 296, 327, 330, 331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228, 235, 268, 274, 296, 327, 330, 331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 235, 268, 274, 296, 327, 330, 331, or any combination thereof, according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution.In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 234, 235, 268, 274, 296, 327, 330, 331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 234, 268, 274, 296, 327, 330, 331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 237, 238, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution.

[0053] In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position C226, P227, P228, C229, P230, A231, P232, E233, L234, L235, G236, G237, P238, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position C226 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P227 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P228 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position C229 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P230 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position A231 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P232 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position E233 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position L234 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position L235 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position G236 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position G237 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P238 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P228, L234, L235, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution.In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions P228 and L234 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions P228 and L235 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions L234 and L235 according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions G237 and P238 according to SEQ ID NO: 88.

[0054] In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions C226, P227, P228, C229, P230, A231, P232, E233, L234, L235, G236, G237, P238, H268, K274, N276, Y296, Y300, L309, A327, A330, P331, A339, or any combination thereof, according to SEQ ID NO: 88, wherein the mutations are insertions, deletions, or substitutions. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at positions P228, L234, L235, H268, K274, N276, Y296, Y300, L309, A327, A330, P331, A339, or any combination thereof, according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at positions P228, L234, L235, H268, K274, Y296, A327, A330, P331, or any combination thereof, according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P228, H268, K274, Y296, A327, A330, P331, or any combination thereof, according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P228, L234, H268, K274, Y296, A327, A330, P331, or any combination thereof, according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions P228, L235, H268, K274, Y296, A327, A330, P331, or any combination thereof, according to SEQ ID NO: 88, wherein the mutations are insertions, deletions, or substitutions.In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position L235, H268, K274, Y296, A327, A330, P331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position L234, L235, H268, K274, Y296, A327, A330, P331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position L234, H268, K274, Y296, A327, A330, P331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at positions P228, L234, L235, H268, K274, Y296, A330, P331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at positions P228, H268, K274, Y296, A330, P331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at positions P228, L234, H268, K274, Y296, A330, P331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions P228, L235, H268, K274, Y296, A330, P331, or any combination thereof, according to SEQ ID NO: 88, wherein the mutations are insertions, deletions, or substitutions.In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position L235, H268, K274, Y296, A330, P331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position L234, L235, H268, K274, Y296, A330, P331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position L234, H268, K274, Y296, A330, P331, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position G237, P238, or any combination thereof according to SEQ ID NO: 88, wherein the mutation is an insertion, deletion, or substitution.

[0055] In some embodiments, the variant Fc domain comprises mutations corresponding to S228P, L234F, L235E, H268Q, K274Q, N276K, Y296F, Y300F, L309V, A327G, A330S, P331S, A339T, or any combination thereof, according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to S228P, L234F, L235E, H268Q, K274Q, Y296F, A327G, A330S, P331S, or any combination thereof, according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to a mutation at position S228P according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to a mutation at position L234F according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at position L235E according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at positions S228P and L234F according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at positions S228P and L235E according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at positions L234F and L235E according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutations S228P, H268Q, K274Q, Y296F, A327G, A330S, P331S, or any combination thereof according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to S228P, L234F, H268Q, K274Q, Y296F, A327G, A330S, P331S, or any combination thereof, according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to S228P, L235E, H268Q, K274Q, Y296F, A327G, A330S, P331S, or any combination thereof, according to SEQ ID NO: 88.In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations according to SEQ ID NO: 88: L235E, H268Q, K274Q, Y296F, A327G, A330S, P331S, or any combination thereof. In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations according to SEQ ID NO: 88: L234F, L235E, H268Q, K274Q, Y296F, A327G, A330S, P331S, or any combination thereof. In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations according to SEQ ID NO: 88: L234F, H268Q, K274Q, Y296F, A327G, A330S, P331S, or any combination thereof. In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations according to SEQ ID NO: 88: S228P, L234F, L235E, H268Q, K274Q, Y296F, A330S, P331S, or any combination thereof. In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations according to SEQ ID NO: 88: S228P, H268Q, K274Q, Y296F, A330S, P331S, or any combination thereof. In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations according to SEQ ID NO: 88: S228P, L234F, H268Q, K274Q, Y296F, A330S, P331S, or any combination thereof. In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations according to SEQ ID NO: 88: S228P, L235E, H268Q, K274Q, Y296F, A330S, P331S, or any combination thereof. In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations according to SEQ ID NO: 88: L235E, H268Q, K274Q, Y296F, A330S, P331S, or any combination thereof. In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations according to SEQ ID NO: 88: L234F, L235E, H268Q, K274Q, Y296F, A330S, P331S, or any combination thereof.In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations according to SEQ ID NO: 88: L234F, H268Q, K274Q, Y296F, A330S, P331S, or any combination thereof.

[0056] In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a mutation at position 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, or any combination thereof according to SEQ ID NO: 89, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a mutation at position 226 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a mutation at position 227 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a mutation at position 228 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a mutation at position 229 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a mutation at position 230 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to the mutation at position 231 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to the mutation at position 232 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to the mutation at position 233 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to the mutation at position 234 according to SEQ ID NO: 89. In some embodiments, the v IgG2 Fc domain comprises a mutation corresponding to the mutation at position 235 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to the mutation at position 236 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to the mutation at position 237 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to the mutation at position 238 according to SEQ ID NO: 89.In some embodiments, the variant IgG2 Fc domain comprises mutations corresponding to mutations at positions 228, 234, 235, or any combination thereof according to SEQ ID NO: 89, wherein the mutations are insertions, deletions, or substitutions. In some embodiments, the variant IgG2 Fc domain comprises mutations corresponding to mutations at positions 228 and 234 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises mutations corresponding to mutations at positions 228 and 235 according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises mutations corresponding to mutations at positions 234 and 235 according to SEQ ID NO: 89.

[0057] In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a mutation at position 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 268, 274, 276, 296, 300, 309, 327, 330, 331, 339, or any combination thereof according to SEQ ID NO: 90, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a mutation at position 226 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a mutation at position 227 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a mutation at position 228 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to the mutation at position 229 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to the mutation at position 230 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to the mutation at position 231 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to the mutation at position 232 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to the mutation at position 233 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to the mutation at position 234 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to the mutation at position 235 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to the mutation at position 236 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to the mutation at position 237 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to the mutation at position 238 according to SEQ ID NO:90.In some embodiments, the variant IgG3 Fc domain comprises mutations corresponding to mutations at positions 228, 234, 235, or any combination thereof according to SEQ ID NO: 90, wherein the mutations are insertions, deletions, or substitutions. In some embodiments, the variant IgG3 Fc domain comprises mutations corresponding to mutations at positions 228 and 234 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises mutations corresponding to mutations at positions 228 and 235 according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises mutations corresponding to mutations at positions 234 and 235 according to SEQ ID NO: 90.

[0058] In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 268, 274, 276, 296, 300, 309, 327, 330, 331, 339, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 226 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 227 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at position 229 according to SEQ ID NO:91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at position 230 according to SEQ ID NO:91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at position 231 according to SEQ ID NO:91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at position 232 according to SEQ ID NO:91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at position 233 according to SEQ ID NO:91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at position 234 according to SEQ ID NO:91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at position 235 according to SEQ ID NO:91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at position 236 according to SEQ ID NO:91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at position 237 according to SEQ ID NO:91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at position 238 according to SEQ ID NO:91.In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions 228, 234, 235, or any combination thereof according to SEQ ID NO: 91, wherein the mutations are insertions, deletions, or substitutions. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions 228 and 234 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions 228 and 235 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions 234 and 235 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions 237 and 238 according to SEQ ID NO: 91.

[0059] In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at positions 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 268, 274, 276, 296, 300, 309, 327, 330, 331, 339, or any combination thereof, according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228, 234, 235, 268, 274, 276, 296, 300, 309, 327, 330, 331, 339, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228, 234, 235, 268, 274, 296, 327, 330, 331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228, 268, 274, 296, 327, 330, 331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228, 234, 268, 274, 296, 327, 330, 331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228, 235, 268, 274, 296, 327, 330, 331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at positions 235, 268, 274, 296, 327, 330, 331, or any combination thereof, according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution.In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 234, 235, 268, 274, 296, 327, 330, 331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 234, 268, 274, 296, 327, 330, 331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 237, 238, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution.

[0060] In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position C226, P227, S228, C229, P230, A231, P232, E233, F234, L235, G236, G237, P238, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position C226 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P227 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position S228 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position C229 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P230 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position A231 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P232 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position E233 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position F234 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position L235 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position G236 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position G237 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P238 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position S228, F234, L235, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution.In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions S228 and F234 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions S228 and L235 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions F234 and L235 according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions G237 and P238 according to SEQ ID NO: 91.

[0061] In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions C226, P227, S228, C229, P230, A231, P232, E233, F234, L235, G236, G237, P238, Q268, Q274, N276, F296, Y300, L309, G327, S330, S331, A339, or any combination thereof, according to SEQ ID NO: 91, wherein the mutations are insertions, deletions, or substitutions. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at positions S228, F234, L235, Q268, Q274, N276, F296, Y300, L309, G327, S330, S331, A339, or any combination thereof, according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at positions S228, F234, L235, Q268, Q274, F296, G327, S330, S331, or any combination thereof, according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position S228, Q268, Q274, F296, G327, S330, S331, or any combination thereof, according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position S228, F234, Q268, Q274, F296, G327, S330, S331, or any combination thereof, according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions S228, L235, Q268, Q274, F296, G327, S330, S331, or any combination thereof, according to SEQ ID NO: 91, wherein the mutations are insertions, deletions, or substitutions.In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position L235, Q268, Q274, F296, G327, S330, S331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position F234, L235, Q268, Q274, F296, G327, S330, S331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position F234, Q268, Q274, F296, G327, S330, S331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position S228, F234, L235, Q268, Q274, F296, S330, S331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position S228, Q268, Q274, F296, S330, S331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position S228, F234, Q268, Q274, F296, S330, S331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at positions S228, L235, Q268, Q274, F296, S330, S331, or any combination thereof, according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution.In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position L235, Q268, Q274, F296, S330, S331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position F234, L235, Q268, Q274, F296, S330, S331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position F234, Q268, Q274, F296, S330, S331, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position G237, P238, or any combination thereof according to SEQ ID NO: 91, wherein the mutation is an insertion, deletion, or substitution.

[0062] In some embodiments, the variant Fc domain comprises mutations corresponding to S228P, F234L, L235E, Q268H, Q274K, N276K, F296Y, Y300F, L309V, G327A, S330A, S331P, A339T, or any combination thereof, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to S228P, F234L, L235E, Q268H, Q274K, F296Y, G327A, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to a mutation at position S228P according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to a mutation at position F234L according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at position L235E according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at positions S228P and F234L according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at positions S228P and L235E according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutation at positions F234L and L235E according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to the mutations S228P, Q268H, Q274K, F296Y, G327A, S330A, S331P, or any combination thereof according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to S228P, F234L, Q268H, Q274K, F296Y, G327A, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to S228P, L235E, Q268H, Q274K, F296Y, G327A, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91.In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations: L235E, Q268H, Q274K, F296Y, G327A, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations: F234L, L235E, Q268H, Q274K, F296Y, G327A, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations: F234L, Q268H, Q274K, F296Y, G327A, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to S228P, F234L, L235E, Q268H, Q274K, F296Y, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to S228P, Q268H, Q274K, F296Y, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to S228P, F234L, Q268H, Q274K, F296Y, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to S228P, L235E, Q268H, Q274K, F296Y, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to L235E, Q268H, Q274K, F296Y, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to F234L, L235E, Q268H, Q274K, F296Y, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91.In some embodiments, the variant Fc domain comprises mutations corresponding to the following mutations according to SEQ ID NO:91: F234L, Q268H, Q274K, F296Y, S330A, S331P, or any combination thereof.

[0063] In some embodiments, the variant Fc polypeptide is a chimeric IgG Fc polypeptide. In some embodiments, the chimeric IgG Fc polypeptide is a chimeric IgG1 / IgG2 polypeptide, a chimeric IgG1 / IgG3 polypeptide, a chimeric IgG1 / IgG4 polypeptide, a chimeric IgG2 / IgG3 polypeptide, a chimeric IgG2 / IgG4 polypeptide, or a chimeric IgG3 / IgG4 polypeptide.

[0064] In some embodiments, the variant Fc polypeptide comprises a mutation in the CH2 region and / or hinge region. In some embodiments, the mutation is a substitution, insertion, or deletion. In some embodiments, a variant Fc polypeptide substitutes a CH2 region of an IgG isotype with a CH2 region of a different IgG isotype. In some embodiments, the variant Fc polypeptide comprises a CH2 domain amino acid sequence having at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identity to SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, or SEQ ID NO:101. In some embodiments, the variant Fc polypeptide comprises a CH2 domain amino acid sequence having at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identity to SEQ ID NO:96. In some embodiments, a variant Fc polypeptide comprises a CH2 domain amino acid sequence at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identical to SEQ ID NO: 97. In some embodiments, a variant Fc polypeptide comprises a CH2 domain amino acid sequence at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identical to SEQ ID NO: 98. In some embodiments, a variant Fc polypeptide comprises a CH2 domain amino acid sequence at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identical to SEQ ID NO: 99. In some embodiments, a variant Fc polypeptide comprises a CH2 domain amino acid sequence at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identical to SEQ ID NO: 100. In some embodiments, the variant Fc polypeptide comprises a CH2 domain amino acid sequence having at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identity to SEQ ID NO:101.

[0065] In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and a mutation at position 228, 234, 235, or any combination thereof, compared to SEQ ID NO: 88, and wherein the variant Fc polypeptide preferentially binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96 and a mutation at position 228, 234, 235, or any combination thereof, compared to SEQ ID NO: 88, and the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 97 and a mutation at position 228, 234, 235, or any combination thereof, compared to SEQ ID NO: 88, and the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα.In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 98 and a mutation at position 228, 234, 235, or any combination thereof, compared to SEQ ID NO: 88, and the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 99 and a mutation at position 228, 234, 235, or any combination thereof, compared to SEQ ID NO: 88, and the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 100 and a mutation at position 228, 234, 235, or any combination thereof, compared to SEQ ID NO: 88, and the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα.In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 101 and a mutation at position 228, 234, 235, or any combination thereof, compared to SEQ ID NO: 88, and the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα.

[0066] In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 14, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and a mutation at position 228 compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and a mutation at position 234 compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and a mutation at position 235 compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα.In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and mutations at positions 228 and 234 compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and mutations at positions 228 and 235 compared to SEQ ID NO: 88, and the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and mutations at positions 234 and 235 compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα.In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and mutations at positions 228, 234, and 235 compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and a mutation of S228P, L234F, L235E, or any combination thereof, compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and a S228P mutation compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα.In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and a L234F mutation compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and an L235E mutation compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and S228P and L234F mutations compared to SEQ ID NO: 88, and the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα.In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and S228P and L235E mutations compared to SEQ ID NO: 88, and the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and L234F and L235E mutations compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα. In some embodiments, the variant Fc polypeptide comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity to SEQ ID NO: 88, provided that the variant Fc polypeptide comprises a CH2 region comprising the sequence of SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, or SEQ ID NO: 101, and the following mutations compared to SEQ ID NO: 88: S228P, L234F, and L235E; and wherein the Fc polypeptide selectively binds FcγRIIβ over FcγRIIα.

[0067] In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations that confer selective binding to FcγRIIβ over FcγRIIα. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations that enhance selective binding to FcγRIIβ over FcγRIIα. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with any one of VFC-1 to VFC-90 as provided in Table 4. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with any one of VFC-1 to VFC-87 as provided in Table 4, and does not comprise the C-terminal lysine (K). [Table 4-1] [Table 4-2] [Table 4-3] [Table 4-4] [Table 4-5] [Table 4-6] [Table 4-7] [Table 4-8] [Table 4-9] [Table 4-10] [Table 4-11] Table 4-12 Table 4-13 Table 4-14 Table 4-15

[0068] In some embodiments, the variant IgG Fc polypeptide is selected from the group consisting of VFC-1, VFC-2, VFC-3, VFC-4, VFC-5, VFC-6, VFC-7, VFC-8, VFC-9, VFC-10, VFC-11, VFC-12, VFC-13, VFC-14, VFC-15, VFC-16, VFC-17, VFC-18, VFC-19, VFC-20, VFC-21, VFC-22, VFC-23, VFC-24, VFC-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC-37, VFC-38, VFC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC-48, VFC-49, VFC-50, VFC-51, VFC-52, VFC-53, VFC-54, VFC-55, VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC-61, VFC-62, VFC-63, VFC-64, VFC-65, VFC-66, VFC-67, VFC-68, VFC-69, VFC-70, VFC-71, VFC-72, VFC-73, VFC-74, VFC-75, VFC-76, VFC-77, VFC-78, VFC-79, VFC-80, VFC-81, VFC-82, VFC-83, VFC-8 FC-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VF C-37, VFC-38, VFC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC-48, VFC -49, VFC-50, VFC-51, VFC-52, VFC-53, VFC-54, VFC-55, VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC- 61, VFC-62, VFC-63, VFC-64, VFC-65, VFC-66, VFC-67, VFC-68, VFC-69, VFC-70, VFC-71, VFC-72, VFC-7 VFC-3, VFC-74, VFC-75, VFC-76, VFC-77, VFC-78, VFC-79, VFC-80, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, VFC-87, VFC-88, VFC-89, VFC-90, or any combination thereof.In some embodiments, VFC-1, VFC-2, VFC-3, VFC-4, VFC-5, VFC-6, VFC-7, VFC-8, VFC-9, VFC-10, VFC-11, VFC-12, VFC-13, VFC-14, VFC-15, VFC-16, VFC-17, VFC-18, VFC-19, VFC-20, VFC-21, VFC-22, VFC-23, VFC-24, VFC-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC-37, VFC-38, VFC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC-48, VFC-49, VFC-50, VFC-51, VFC-52, VFC-53, VFC-54, VFC-55, VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC-61, VFC-62, VFC-63, VFC-64, VFC-65, VFC-66, VFC-67, VFC-68, VFC-69, VFC-70, VFC-71, VFC-72, VFC-73, VFC-74, VFC-75, VFC-76, VFC-77, VFC-78, VFC-79, VFC-80, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, FC-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC -37, VFC-38, VFC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC-48, VFC-49 , VFC-50, VFC-51, VFC-52, VFC-53, VFC-54, VFC-55, VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC-61, V FC-62, VFC-63, VFC-64, VFC-65, VFC-66, VFC-67, VFC-68, VFC-69, VFC-70, VFC-71, VFC-72, VFC-73, VFC The variant IgG Fc polypeptides comprising one or more mutations selected from mutations associated with any one of VFC-74, VFC-75, VFC-76, VFC-77, VFC-78, VFC-79, VFC-80, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, VFC-87, VFC-88, VFC-89, VFC-90, or any combination thereof, have increased binding affinity for FcγRIIβ over FcγRIIα compared to that of wild-type IgG.

[0069] In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-1. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-2. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-3. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-4. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-5. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-6. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-7. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-8. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-9. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-10. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-11. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-12. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-13. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-14. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-15.In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-16. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-27. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-28. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-29. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-30. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-31. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-32. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-33. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-34. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-35. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-36. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-37. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-38. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-39. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-40. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-41.In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-42. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-43. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-44. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-45. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-46. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-47. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-48. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-49. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-50. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-51. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-52. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-53. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-54. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-55. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-56. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-57.In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-58. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-59. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-60. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-61. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-62. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-63. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-64. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-65. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-66. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-67. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-68. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-69. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-70. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-71. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-72. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-73.In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-74. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-75. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-76. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-77. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-78. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-79. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-80. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-81. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-82. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-83. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-84. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-85. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-86. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-87. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-88. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-89.In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-90.

[0070] In some embodiments, the mutation is a substitution, insertion, or deletion, hi some embodiments, the insertion may be of 1 to 5 residues, or more.

[0071] In some embodiments, the variant IgG Fc polypeptide comprises a mutation selected from a mutation at one or more of positions selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330, and any combination thereof (according to EU numbering) relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 233 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 234 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 235 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 237 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 238 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 239 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 240 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 268 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 269 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 270 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 271 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 329 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 330 compared to SEQ ID NO: 88.

[0072] In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 238, 269, 270, or 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 238, 269, 270, and 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 237, 238, 269, 270, or 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 237, 238, 269, 270, and 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 237, 238, 269, 270, or 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 237, 238, 239, 269, 270, and 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 237, 238, 240, 269, 270, or 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 237, 238, 240, 269, 270, and 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 235, 238, 269, 270, or 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 235, 238, 269, 270, and 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 233, 235, 238, 269, 270, or 330 relative to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 233, 235, 238, 269, 270, and 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 235, 238, 269, 270, or 330, and an insertion between positions 233 and 234, relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 235, 238, 269, 270, and 330, and an insertion between positions 233 and 234, relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 234, 235, 268, 271, or 329, relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 234, 235, 268, 271, and 329 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 234, 235, 239, 268, 271, or 329 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 234, 235, 239, 268, 271, and 329 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 234 or 235 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 234 and 235 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 237 and 238 relative to SEQ ID NO: 88.

[0073] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide is selected from the group consisting of VFC-1, VFC-2, VFC-3, VFC-4, VFC-5, VFC-6, VFC-7, VFC-8, VFC-9, VFC-10, VFC-11, VFC-12, VFC-13, VFC-14, VFC-15, VFC-16, VFC-17, VFC-18, VFC-19, VFC-20, VFC-21, VFC-22, VFC-23, VFC-24 , VFC-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36 , VFC-37, VFC-38, VFC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC-48, VFC-49, VFC-50, VFC-51, VFC-52, VFC-53, VFC-54, VFC-55, VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC-61, VFC-62, VFC-63, VFC-64, VFC-65, VFC-66, VFC-67, VFC-68, VFC-69, VFC-70, VFC-71, VFC-72, V VFC-73, VFC-74, VFC-75, VFC-76, VFC-77, VFC-78, VFC-79, VFC-80, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, VFC-87, VFC-88, VFC-89, or VFC-90. Non-limiting examples include variant IgG Fc polypeptides comprising an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide is selected from the group consisting of VFC-1, VFC-2, VFC-3, VFC-4, VFC-5, VFC-6, VFC-70, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, VFC-87, VFC-88, VFC-89, or VFC-90.VFC-7, VFC-8, VFC-9, VFC-10, VFC-11, VFC-12, VFC-13, VFC-14, VFC-15, VFC-16, VFC-17, VFC-1 8, VFC-19, VFC-20, VFC-21, VFC-22, VFC-23, VFC-24, VFC-25, VFC-26, VFC-27, VFC-28, VFC-29, V FC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC-37, VFC-38, VFC-39, VFC-40, VFC -41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC-48, VFC-49, VFC-50, VFC-51, VFC-52 , VFC-53, VFC-54, VFC-55, VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC-61, VFC-62, VFC-63, V FC-64, VFC-65, VFC-66, VFC-67, VFC-68, VFC-69, VFC-70, VFC-71, VFC-72, VFC-73, VFC-74, VFC- VFC-75, VFC-76, VFC-77, VFC-78, VFC-79, VFC-80, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, VFC-87, VFC-88, VFC-89, or VFC-90, provided that the variant IgG comprises one or more mutations selected from the mutations associated with any one of VFC-75, VFC-76, VFC-77, VFC-78, VFC-79, VFC-80, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, VFC-87, VFC-88, VFC-89, or VFC-90. Fc polypeptides include VFC-1, VFC-2, VFC-3, VFC-4, VFC-5, VFC-6, VFC-7, VFC-8, VFC-9, VFC-10, VFC-11, VFC-12, VFC- 13, VFC-14, VFC-15, VFC-16, VFC-17, VFC-18, VFC-19, VFC-20, VFC-21, VFC-22, VFC-23, VFC-24, VFC-25, VFC -26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC-37, VFC-38, V FC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC-48, VFC-49, VFC-50, VFC-51,VFC-52, VFC-53, VFC-54, VFC-55, VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC-61, VFC-62, VFC-63, VFC-64, VFC-65, VFC-66, VFC-67, VFC-68, VFC- 69, VFC-70, VFC-71, VFC-72, VFC-73, VFC-74, VFC-75, VFC-76, VFC-77, VFC-78, VFC-79, VFC-80, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, V one or more mutations selected from mutations associated with any one of VFC-87, VFC-88, VFC-89, or VFC-90, and one or more mutations associated with any one of VFC-1, VFC-2, VFC-3, VFC-4, VFC-5, VFC-6, VFC-7, VFC-8, VFC-9, VFC-10, VFC-11, VFC-12, VFC-13, VFC-14, VFC-15, VFC-16, VFC-17, VFC-18, VFC-19, VFC-20, VFC-21, VFC-22, VFC-23, VFC-24, VFC-25, VFC-26, VFC-27, VFC- 28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC-37, VFC-38, VFC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, V FC-46, VFC-47, VFC-48, VFC-49, VFC-50, VFC-51, VFC-52, VFC-53, VFC-54, VFC-55, VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC-61, VFC-62, VFC-6 3, VFC-64, VFC-65, VFC-66, VFC-67, VFC-68, VFC-69, VFC-70, VFC-71, VFC-72, VFC-73, VFC-74, VFC-75, VFC-76, VFC-77, VFC-78, VFC-79, VFC-80, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, VFC-87, VFC-88, VFC-89, or VFC-90.

[0074] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide is not selected from the group consisting of VFC-1, VFC-2, VFC-3, VFC-4, VFC-5, VFC-6, VFC-7, VFC-8, VFC-9, VFC-10, VFC-11, VFC-12, VFC-13, VFC-14, VFC-15, VFC-16, VFC-17, VFC-18, VFC-19, VFC-20, VFC-21, VFC-22, VFC-23, VFC-24, VFC-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC-37, VFC-38, VFC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC-48, VFC-49, VFC-50, VFC-51, VFC-52, VFC-53, VFC-54, VFC-55, VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC-61, VFC-62, VFC-63, VFC-64, VFC-65, VFC-66 C-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC -37, VFC-38, VFC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC-48, VFC-4 9, VFC-50, VFC-51, VFC-52, VFC-53, VFC-54, VFC-55, VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC-61 , VFC-62, VFC-63, VFC-64, VFC-65, VFC-66, VFC-67, VFC-68, VFC-69, VFC-70, VFC-71, VFC-72, VFC-73, V provided that the gene contains one or more mutations selected from mutations associated with any one of VFC-74, VFC-75, VFC-76, VFC-77, VFC-78, VFC-79, VFC-80, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, VFC-87, VFC-88, VFC-89, VFC-90, or a combination thereof.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-1. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-2. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-3. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-4. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-5.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-6. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-7. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-8. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-9. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-10.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-11. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-12. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-13. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-14. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-15. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-16. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-17. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-18.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-19. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-20. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-21. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-22. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-23.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-24. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-25. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-26. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-27. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-28.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-29. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-30. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-31. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-32. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-33. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-34. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-35.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-36. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-37. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-38. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-39. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-40.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-41. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-42. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-43. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-44. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-45. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-46. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-47. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-48. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-49.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-50. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-51. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-52. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-53. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-54.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-55. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-56. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-57. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-58. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-59.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-60. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-61. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-62. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-63. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-64. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from mutations associated with VFC-65. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-66.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-67. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-68. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-69. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-70. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-71.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-72. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-73. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-74. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-75. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-76.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-77. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-77. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-79. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-80. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-81. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-82. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-83. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-84.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-85. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-86. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-87. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-89.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises one or more mutations selected from those associated with VFC-90.

[0075] Non-limiting examples of variant IgG Fc polypeptides comprising an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation selected from a mutation at one or more of positions selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330, and any combination thereof, compared to SEQ ID NO: 88. Non-limiting examples of Fc polypeptides include variant IgG Fc polypeptides comprising one or more mutations in the amino acid sequence that are not mutations selected from a mutation at one or more of positions selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330, and any combination thereof, relative to SEQ ID NO: 88, and a mutation at one or more of positions selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330, and any combination thereof, relative to SEQ ID NO: 14.

[0076] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation selected from a mutation at one or more of positions selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330, and any combination thereof, compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position 233 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position 234 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position 235 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position 237 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position 238 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position 239 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position 240 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position 268 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at position 269 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position 270 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position 271 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position 329 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position 330 compared to SEQ ID NO: 88.

[0077] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 238, 269, 270, or 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises the set of mutations at positions 238, 269, 270, and 330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 237, 238, 269, 270, or 330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions 237, 238, 269, 270, and 330 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 237, 238, 239, 269, 270, or 330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions 237, 238, 239, 269, 270, and 330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 237, 238, 240, 269, 270, or 330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions 237, 238, 240, 269, 270, and 330 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 235, 238, 269, 270, or 330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions 235, 238, 269, 270, and 330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 233, 235, 238, 269, 270, or 330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions 233, 235, 238, 269, 270, and 330 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 235, 238, 269, 270, or 330, and an insertion between positions 233 and 234, compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions 235, 238, 269, 270, and 330, and an insertion between positions 233 and 234, compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 234, 235, 268, 271, or 329 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions 234, 235, 268, 271, and 329 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 234, 235, 239, 268, 271, or 329 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a set of mutations at positions 234, 235, 239, 268, 271, and 329 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 234 or 235 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 234 and 235 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from 237 or 237 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 237 and 238 relative to SEQ ID NO: 88.

[0078] In some embodiments, the variant IgG Fc polypeptide comprises a mutation selected from a mutation at one or more of positions selected from 233, L234, L235, G237, P238, S239, V240, H268, E269, D270, P271, P329, A330, and any combination thereof, relative to SEQ ID NO: 14. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 233 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position L234 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position L235 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position G237 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position P238 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position S239 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position V240 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position H268 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position E269 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position D270 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position P271 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position P329 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position A330 compared to SEQ ID NO: 88.

[0079] In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from P238, E269, D270, or A330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions P238, E269, D270, and A330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from G237, P238, E269, D270, or A330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions G237, P238, E269, D270, and A330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from G237, P238, S239, E269, D270, or A330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions G237, P238, S239, E269, D270, and A330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from G237, P238, V240, E269, D270, or A330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions G237, P238, V240, E269, D270, and A330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from L235, P238, E269, D270, or A330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions L235, P238, E269, D270, and A330 relative to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from E233, L235, P238, E269, D270, or A330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions E233, L235, P238, E269, D270, and A330 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from L235, P238, E269, D270, or A330 relative to SEQ ID NO: 88, and an insertion between positions E233 and L234. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions L235, P238, E269, D270, and A330, and an insertion between positions 233 and L234, relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from L234, L235, H268, P271, or P329, relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions L234, L235, H268, P271, and P329, relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from L234, L235, S239, H268, P271, or P329, relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions L234, L235, S239, H268, P271, and P329 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more positions selected from L234 or L235 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions L234 and L235 relative to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions G237 and P238 compared to SEQ ID NO:88.

[0080] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises mutations selected from a mutation at one or more of positions selected from E233, L234, L235, G237, P238, S239, V240, H268, E269, D270, P271, P329, A330, and any combination thereof, compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at position E233 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at position L234 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at position L235 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position G237 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position P238 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position S239 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position V240 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at position H268 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position E269 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position D270 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position P271 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a mutation at position P329 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at position A330 compared to SEQ ID NO: 88.

[0081] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from P238, E269, D270, or A330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions P238, E269, D270, and A330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from G237, P238, E269, D270, or A330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions G237, P238, E269, D270, and A330 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from G237, P238, S239, E269, D270, or A330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions G237, P238, S239, E269, D270, and A330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from G237, P238, V240, E269, D270, or A330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions G237, P238, V240, E269, D270, and A330 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from L235, P238, E269, D270, or A330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions L235, P238, E269, D270, and A330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from E233, L235, P238, E269, D270, or A330 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions E233, L235, P238, E269, D270, and A330 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from L235, P238, E269, D270, or A330, and an insertion between positions E233 and L234, compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions L235, P238, E269, D270, and A330, and an insertion between positions E233 and L234, compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from L234, L235, H268, P271, or P329 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions L234, L235, H268, P271, and P329 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from L234, L235, S239, H268, P271, or P329 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the set of mutations at positions L234, L235, S239, H268, P271, and P329 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from L234 or L235 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions L234 and L235 relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of positions selected from G237 or P238 compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions G237 and P238 compared to SEQ ID NO:88.

[0082] In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from L234F, L235E, L235V, G237D, G237E, P238D, P238G, P238E, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof, relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a L234F mutation relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a L235E mutation relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a L235V mutation relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a G237D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a G237E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a P238D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a P238G mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a P238E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a S239G mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a S239D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a V240A mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a H268D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an E269D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a D270E mutation compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises a P271G mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a P329A mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a A330R mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an insertion of the amino acid sequence GEV between positions 233 and 234 compared to SEQ ID NO: 88.

[0083] In some embodiments, the variant IgG Fc polypeptide is a set of mutations P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations, relative to SEQ ID NO: 88, of G237D, P238G, V240A, E269D, D270E, and A330R; a set of mutations compared to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R; A set of mutations compared to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234; a set of mutations P238S, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G; a set of mutations, relative to SEQ ID NO: 88, of G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G; a set of mutations compared to SEQ ID NO: 88: P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G; A set of mutations L234F and L235E compared to SEQ ID NO: 88; a set of mutations G237E and P238E compared to SEQ ID NO: 88; or The set of mutations may be selected from any combination thereof.

[0084] In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: P238D, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: G237D, P238G, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: G237D, P238S, S239G, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: G237D, P238G, V240A, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234. In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: P238S, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G. In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G. In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: L234F and L235E. In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: G237E and P238E.In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G. In some embodiments, the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G.

[0085] In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises one or more mutations selected from L234F, L235E, L235V, G237D, G237E, P238D, P238G, P238E, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof, relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the mutation L234F relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a L235E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a L235V mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a G237D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a G237E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a P238D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a P238G mutation compared to SEQ ID NO:88.In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a P238E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a S239G mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a S239D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a V240A mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a H268D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises an E269D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a D270E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a P271G mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a P329A mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises an A330R mutation compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises an insertion of the amino acid sequence GEV between positions 233 and 234 compared to SEQ ID NO: 88.

[0086] In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide is a set of mutations P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations, relative to SEQ ID NO: 88, of G237D, P238G, V240A, E269D, D270E, and A330R; a set of mutations compared to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R; A set of mutations compared to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234; a set of mutations P238S, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G; a set of mutations G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 14; or a set of mutations P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 14; A set of mutations L234F and L235E compared to SEQ ID NO: 88; a set of mutations G237E and P238E compared to SEQ ID NO: 88; or The set of mutations may be selected from any combination thereof.

[0087] In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: P238D, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: G237D, P238G, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: G237D, P238S, S239G, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: G237D, P238G, V240A, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: P238S, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G.In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: L234F and L235E. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: G237E and P238E. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations relative to SEQ ID NO: 88: P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G.

[0088] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises one or more mutations selected from: L234F, L235E, L235V, G237D, G237E, P238D, P238G, P238E, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof, relative to SEQ ID NO: 88.

[0089] Non-limiting examples of variant IgG Fc polypeptides include an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG a variant IgG, provided that the Fc polypeptide comprises, relative to SEQ ID NO: 88, mutations at one or more positions selected from: L234F, L235E, L235V, G237D, G237E, G237E, P238D, P238G, P238E, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof. Non-limiting examples of Fc polypeptides include mutations at one or more positions selected from L234F, L235E, L235V, G237D, G237E, P238D, P238G, P238E, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof, relative to SEQ ID NO: 88; 8, the variant IgG Fc polypeptides include one or more mutations in the amino acid sequence that is not a mutation selected from: L234F, L235E, L235V, G237D, G237E, P238D, P238G, P238E, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof.

[0090] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a L234F mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a L234F mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a L235E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a L235E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a G237D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a G237D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a G237E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a G237E mutation compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a P238D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a P238D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a P238G mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a P238G mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a P238E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a P238E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a S239G mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a S239G mutation compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a S239D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a S239D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a V240A mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a V240A mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a H268D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a H268D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises an E269D mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an E269D mutation compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a D270E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a D270E mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises a P271G mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a P271G mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a P329A mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a P329A mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises an A330R mutation compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an A330R mutation compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises an insertion of the amino acid sequence GEV between positions 233 and 234 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an insertion of the amino acid sequence GEV between positions 233 and 234 compared to SEQ ID NO: 88.

[0091] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide is a set of mutations P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations, relative to SEQ ID NO: 88, of G237D, P238G, V240A, E269D, D270E, and A330R; a set of mutations compared to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R; A set of mutations compared to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234; a set of mutations P238S, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G; a set of mutations G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 14; a set of mutations P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 14; A set of mutations L234F and L235E compared to SEQ ID NO: 88; a set of mutations G237E and P238E compared to SEQ ID NO: 88; or The set of mutations may be selected from any combination thereof.

[0092] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: P238D, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: G237D, P238G, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: G237D, P238S, S239G, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: G237D, P238G, V240A, E269D, D270E, and A330R.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: P238S, E269D, D270E, and A330R. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: L234F and L235E. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: G237E and P238E. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G.

[0093] In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from: L234F, L235E, L235V, G237D, G237E, P238D, P238G, P238E, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof, relative to SEQ ID NO: 14, wherein the variant IgG Fc polypeptide further comprises at least, about, or exactly 1 to 10, 1 to 20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations relative to SEQ ID NO: 88.

[0094] Non-limiting examples include variant IgG Fc polypeptides comprising one or more mutations selected from L234F, L235E, L235V, G237D, G237E, P238D, P238G, P238E, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof, relative to SEQ ID NO: 88; the Fc polypeptide further comprises at least, about, or exactly 1 to 10, 1 to 20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88; The Fc polypeptide may have one or more mutations selected from L234F, L235E, L235V, G237D, G237E, P238D, P238G, P238E, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof, compared to SEQ ID NO: 88; and one or more mutations selected from L234F, L235E, L235V, G237D, G237E, P238D, P238G, P238E, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof, compared to SEQ ID NO: 88. 38D, P238G, P238E, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof.

[0095] In some embodiments, the variant IgG Fc polypeptide comprises a L234F mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a L235E mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a L235V mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a G237D mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a G237E mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises a P238D mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a P238G mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a P238E mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a S239G mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the mutation S239D compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises a V240A mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a H268D mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 14. In some embodiments, the variant IgG Fc polypeptide comprises an E269D mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a D270E mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a P271G mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises a P329A mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an A330R mutation compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises an insertion of the amino acid sequence GEV between positions 233 and 234 compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1 to 10, 1 to 20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88.

[0096] In some embodiments, the variant IgG Fc polypeptide is a set of mutations P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations, relative to SEQ ID NO: 88, of G237D, P238G, V240A, E269D, D270E, and A330R; a set of mutations compared to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R; A set of mutations compared to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234; a set of mutations P238S, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G; a set of mutations G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 14; a set of mutations P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 14; A set of mutations L234F and L235E compared to SEQ ID NO: 88; a set of mutations G237E and P238E compared to SEQ ID NO: 88; or and a set of mutations selected from any combination thereof, wherein the variant IgG Fc polypeptide further comprises, in addition to the set of mutations, at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations compared to SEQ ID NO: 88.

[0097] In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations G237D, P238G, V240A, E269D, D270E, and A330R compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations L235V, P238E, E269D, D270E, and A330R compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations L235V, P238D, E269D, D270E, and A330R and an insertion of the amino acid sequence GEV between positions 233 and 234 relative to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1 to 10, 1 to 20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations relative to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations P238S, E269D, D270E, and A330R compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations L234F and L235E compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations G237E and P238E compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1 to 10, 1 to 20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1 to 10, 1 to 20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88.

[0098] In some embodiments, the variant IgG Fc polypeptide comprises a mutation in the CH2 region and / or hinge region. In some embodiments, the mutation is a substitution, insertion, or deletion. In some embodiments, substitution comprises swapping the CH2 region with a CH2 region of another IgG isotype. In some embodiments, the variant Fc molecule comprises a CH2 domain sequence having at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identity to SEQ ID NOs: 96-101. In some embodiments, the variant Fc molecule comprises a CH2 domain sequence having at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identity to SEQ ID NO: 96. In some embodiments, the variant Fc molecule comprises a CH2 domain sequence having at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identity to SEQ ID NO: 97. In some embodiments, the variant Fc molecule comprises a CH2 domain sequence having at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identity to SEQ ID NO: 98. In some embodiments, the variant Fc molecule comprises a CH2 domain sequence having at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identity to SEQ ID NO: 99. In some embodiments, the variant Fc molecule comprises a CH2 domain sequence having at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identity to SEQ ID NO: 100. In some embodiments, the variant Fc molecule comprises a CH2 domain sequence having at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identity to SEQ ID NO: 101.

[0099] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide is a set of mutations P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations, relative to SEQ ID NO: 88, of G237D, P238G, V240A, E269D, D270E, and A330R; a set of mutations compared to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R; A set of mutations compared to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234; a set of mutations P238S, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G; A set of mutations L234F and L235E compared to SEQ ID NO: 88; a set of mutations G237E and P238E compared to SEQ ID NO: 88; or and a set of mutations selected from any combination thereof, The variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.

[0100] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: P238D, E269D, D270E, and A330R; and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: G237D, P238G, E269D, D270E, and A330R; and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: G237D, P238S, S239G, E269D, D270E, and A330R; and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: G237D, P238G, V240A, E269D, D270E, and A330R; and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R; and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises the following mutation set compared to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234; and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: P238S, E269D, D270E, and A330R; and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G; and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G; and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following mutations compared to SEQ ID NO: 88: L234F and L235E; and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises the following mutations compared to SEQ ID NO: 88: G237E and P238E; and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.

[0101] In some embodiments, the variant IgG Fc polypeptide is a set of mutations P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations, relative to SEQ ID NO: 88, of G237D, P238G, V240A, E269D, D270E, and A330R; a set of mutations compared to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R; A set of mutations compared to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234; a set of mutations P238S, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G; A set of mutations L234F and L235E compared to SEQ ID NO: 88; a set of mutations G237E and P238E compared to SEQ ID NO: 88; or and wherein the variant IgG Fc polypeptide further comprises, in addition to the set of mutations, at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations compared to SEQ ID NO: 88; and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.

[0102] In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88, wherein the variant IgG Fc polypeptide further comprises, in addition to the set of mutations, at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations compared to SEQ ID NO: 88, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88, wherein the variant IgG Fc polypeptide further comprises, in addition to the set of mutations, at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations compared to SEQ ID NO: 88, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO: 88, wherein the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations G237D, P238G, V240A, E269D, D270E, and A330R compared to SEQ ID NO: 88, wherein the variant IgG Fc polypeptide further comprises, in addition to the set of mutations, at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations compared to SEQ ID NO: 88, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations L235V, P238E, E269D, D270E, and A330R compared to SEQ ID NO: 88, wherein the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234, relative to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises at least, about, or exactly 1 to 10, 1 to 20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations relative to SEQ ID NO: 88; The Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations P238S, E269D, D270E, and A330R compared to SEQ ID NO: 88, wherein the variant IgG Fc polypeptide further comprises, in addition to the set of mutations, at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations compared to SEQ ID NO: 88, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 88, wherein the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88, wherein the variant IgG Fc polypeptide further comprises, in addition to the set of mutations, at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations compared to SEQ ID NO: 88, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations L234F and L235E compared to SEQ ID NO: 88, the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises the set of mutations G237E and P238E compared to SEQ ID NO: 88, the variant IgG Fc polypeptide further comprises at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations in addition to the set of mutations compared to SEQ ID NO: 88, and the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.

[0103] In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide is a set of mutations P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations, relative to SEQ ID NO: 88, of G237D, P238G, V240A, E269D, D270E, and A330R; a set of mutations compared to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R; A set of mutations compared to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234; a set of mutations P238S, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G; A set of mutations L234F and L235E compared to SEQ ID NO: 88; a set of mutations G237E and P238E compared to SEQ ID NO: 88; or a set of mutations selected from any combination thereof; The variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.

[0104] In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: P238D, E269D, D270E, and A330R, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: G237D, P238G, E269D, D270E, and A330R, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: G237D, P238S, S239G, E269D, D270E, and A330R, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: G237D, P238G, V240A, E269D, D270E, and A330R, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: P238S, E269D, D270E, and A330R, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following set of mutations compared to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the following mutations compared to SEQ ID NO: 88: L234F and L235E, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a set of mutations G237E and P238E compared to SEQ ID NO: 88, and wherein the variant IgG Fc polypeptide further comprises a CH2 region comprising an amino acid sequence that is at least 50, 60, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 96-101.

[0105] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising an amino acid sequence selected from any one of those provided in Table 4. In some embodiments, the variant IgG The Fc polypeptides are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO:104.

[0106] In some embodiments, SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52 , SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO:104. The Fc polypeptide has increased binding affinity for FcγRIIβ over FcγRIIα compared to that of wild-type IgG.In some embodiments, SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO: Variant IgG Fc polypeptides comprising the amino acid sequence of SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO:104 have increased binding affinity for FcγRIIβ over FcγRIIα compared to that of wild-type IgG.

[0107] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 1. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO:3. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 5. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 7. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO:8.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 9. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 10. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 11. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 12. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 13. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 14. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 15. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 16.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 17. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 18. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 19. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 20. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 21. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 22. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 23. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 24.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 25. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 26. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 27. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 28. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 29. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 30. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 31. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 32. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 33. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 34. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 35.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 36. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 37. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 38. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 39. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 40. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 41. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 42. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO:43.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 44. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 45. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 46. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 47. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 48. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 49. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 50. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO:51.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 52. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 53. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 54. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 56. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 57. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO:59.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 60. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 61. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 62. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 63. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 65. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 66. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 67.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 68. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 69. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO:70. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 71. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 72. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 73. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 74. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 75.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO:76. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 77. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 78. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 79. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 80. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 81. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 82. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 83. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 84.In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 85. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 86. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 87. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 102. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 103. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 104.

[0108] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence selected from any one of those provided in Table 4. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO:104. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO:2. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO:3. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO:4. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 5. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 6.In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 8. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 10. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 11. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 13. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 14. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 15. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 16. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 18. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 19. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 21. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 22. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 24. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 25. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 26.In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 27. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 28. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 29. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 30. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 31. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 32. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 33. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 34. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 35. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 36. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 37. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 38. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 39. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 40. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 41. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 42. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 43. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 44. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 45. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 46.In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 47. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 48. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 49. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 50. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 51. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 52. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 53. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 54. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 55. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 56. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 57. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 58. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 59. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 60. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 61. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 62. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 63. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 65.In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 66. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 67. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 68. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 69. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 70. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 71. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 72. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 73. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 74. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 75. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 76. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 77. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 78. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 79. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 80. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 82. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 83. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 84. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 85.In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 86. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 87. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 103. In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 104.

[0109] In some embodiments, the variant IgG Fc polypeptides provided herein in Table 4 have mutations that enhance or confer preferential binding to FcγRIIβ over FcγRIIα. In some embodiments, the mutation that enhances or confer preferential binding to FcγRIIβ over FcγRIIα is any one of those associated with VFC-1 through VFC-90.

[0110] Dimeric variant Fc molecules In some embodiments, two (or more) linkers associate, either covalently or non-covalently, to form, for example, a hetero- or homodimeric therapeutic compound. In some embodiments, the linker can comprise an Fc region and two Fc regions associated with each other. In some embodiments of therapeutic compounds comprising two linker regions, the linker regions can self-associate, e.g., as two identical Fc regions. In some embodiments of therapeutic compounds comprising two linker regions, the linker regions are unable to self-associate or are substantially unable to self-associate, e.g., the two Fc regions can be members of a knob and hole pair. In some embodiments, the polypeptide comprises a first polypeptide and a second polypeptide. In some embodiments, the first polypeptide comprises a knob mutation and the second polypeptide comprises a hole mutation. In some embodiments, the first polypeptide comprises a hole mutation and the second polypeptide comprises a knob mutation. In some embodiments, the knob mutation is such as provided herein. In some embodiments, the hole mutation is such as provided herein. In some embodiments, the knob mutation is such as provided in any one of SEQ ID NOs: 75, 78, 79, 80, 82, 84, 85, 86, or 87. In some embodiments, the hole mutation is such as provided in any one of SEQ ID NOs: 76, 77, 81, or 83.

[0111] In some embodiments, a polypeptide can associate with another polypeptide. In some embodiments, a polypeptide associated with another polypeptide forms a dimeric molecule.

[0112] In some embodiments, the dimer is a homodimeric molecule. In some embodiments, the dimer is a heterodimeric molecule.

[0113] As used herein, the term "non-covalently bound" can mean that a polypeptide is tethered to another polypeptide through a linker. In some embodiments, the linker is a peptide linker. Non-limiting examples of peptide linkers that can be used are known in the art and are provided herein.

[0114] As discussed herein, different domains, molecules, or polypeptides can be linked together with a linker domain or region. Any linker region described herein can be used as a linker. The linker can be, for example, a glycine / serine linker. In some embodiments, the linker can include one or more repeats of GGGGS (SEQ ID NO: 105). In some embodiments, the linker includes 1, 2, 3, 4, or 5 repeats. In some embodiments, the linker includes GGGGSGGGGS (SEQ ID NO: 106). In some embodiments, the linker includes GGGSGGGGSGGGGGS (SEQ ID NO: 107). In some embodiments, the linker includes GGGGS (SEQ ID NO: 105), (GGGGS)3 (SEQ ID NO: 107), (GGGGS) n (n=1, 2, 3, 4) (SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108)), (Gly)8 (SEQ ID NO: 109) 、 (Gly)6 (SEQ ID NO: 110) 、 (EAAAK)3 (SEQ ID NO: 111), (EAAK) n (n=1-3) (SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114), A(EAAAK)4ALEA(EAAAK)4A (SEQ ID NO: 115), or AEAAAKEAAAKA (SEQ ID NO: 116). These linkers can be used in any of the compounds or compositions provided herein.

[0115] These peptide linkers are non-limiting examples and other peptide linkers can also be used.

[0116] In some embodiments, the polypeptide forms a dimer. In some embodiments, the dimer is a homodimer. In some embodiments, the dimer is a heterodimer.

[0117] Non-limiting exemplary compositions of therapeutic compounds include the following (e.g., in order from N-terminus to C-terminus): R1 - Linker region A-R2 R3 - linker region B-R4, wherein R1, R2, R3, and R4 each independently comprise or are absent an effector binding / modulating moiety, e.g., an anti-PD1 antibody, an anti-LAG3 antibody, an anti-CTLA4 antibody, an anti-FcγRIIb antibody; Linker region A and linker region B comprise moieties that can associate with each other, for example, linker A and linker region B each comprise an Fc polypeptide, provided that an effector binding / modulating moiety and a specific targeting moiety are present. Furthermore, linker region A and linker region B each comprise an Fc polypeptide that is selective for FcγRIIb. In some embodiments, an Fc polypeptide that is selective for FcγRIIb has increased selectivity for FcγRIIb. In some embodiments, an Fc polypeptide that is selective for FcγRIIb has increased affinity for FcγRIIb. In some embodiments, an Fc polypeptide that is selective for FcγRIIb has increased selectivity and affinity for FcγRIIb. In some embodiments, an Fc polypeptide that is selective for FcγRIIb has increased selectivity for FcγRIIb over FcγRIIa. In some embodiments, an Fc polypeptide that is selective for FcγRIIb has increased affinity for FcγRIIb over FcγRIIa. In some embodiments, an Fc polypeptide that is selective for FcγRIIb has increased selectivity and affinity for FcγRIIb over FcγRIIa. In some embodiments, linker region A and linker region B are both absent.

[0118] In some embodiments, the dimer is R1 - Linker region A-R2 R3 - linker region B-R4, including the formula: R1, R2, R3, and R4 each independently comprise or are absent an effector binding / modulating moiety, e.g., an anti-PD1 antibody, an anti-LAG3 antibody, an anti-CTLA4 antibody, an anti-FcγRIIb antibody; Linker region A and linker region B each independently comprise an Fc polypeptide, provided that an effector binding / modulating moiety is present, wherein the Fc polypeptide selectively binds FcγRIIb.

[0119] In some embodiments, R1 comprises or is absent an effector-binding / modulating moiety, e.g., an anti-PD-1 antibody, or antigen-binding fragment thereof, an anti-LAG3 antibody, an anti-CTLA4 antibody, or an anti-FcγRIIb antibody; R2 comprises an effector-binding / modulating moiety, e.g., an anti-PD-1 antibody, or an antigen-binding fragment thereof, an anti-LAG3 antibody, an anti-CTLA4 antibody, or an anti-FcγRIIb antibody; R3 comprises or is absent an effector-binding / modulating moiety, e.g., an anti-PD-1 antibody, or antigen-binding fragment thereof, an anti-LAG3 antibody, an anti-CTLA4 antibody, or an anti-FcγRIIb antibody; R4 comprises an effector-binding / modulating moiety, e.g., an anti-PD-1 antibody, or an antigen-binding fragment thereof, an anti-LAG3 antibody, an anti-CTLA4 antibody, or an anti-FcγRIIb antibody; Linker region A and linker region B comprise moieties that can associate with each other, for example, linker A and linker region B each comprise an Fc polypeptide, provided that one of R1 or R3 is present and one of R2 or R4 is present. Furthermore, linker region A and linker region B each comprise an Fc polypeptide that is selective for FcγRIIb. In some embodiments, an Fc polypeptide that is selective for FcγRIIb has increased selectivity for FcγRIIb. In some embodiments, an Fc polypeptide that is selective for FcγRIIb has increased affinity for FcγRIIb. In some embodiments, an Fc polypeptide that is selective for FcγRIIb has increased selectivity and affinity for FcγRIIb. In some embodiments, an Fc polypeptide that is selective for FcγRIIb has increased selectivity for FcγRIIb over FcγRIIa. In some embodiments, Fc polypeptides that are selective for FcγRIIb have increased affinity for FcγRIIb over FcγRIIa, hi some embodiments, Fc polypeptides that are selective for FcγRIIb have increased selectivity and affinity for FcγRIIb over FcγRIIa.

[0120] In some embodiments, linker region A is selected from the group consisting of VFC-1, VFC-2, VFC-3, VFC-4, VFC-5, VFC-6, VFC-7, VFC-8, VFC-9, VFC-10, VFC-11, VFC-12, VFC-13, VFC-14, VFC-15, VFC-16, VFC-17, VFC-18, VFC-19, VFC-20, VFC-21, VFC-22, VFC-23, VFC-24, VFC-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC-37, VFC-38, VFC-39, VFC-40, VFC-41, VFC- FC-20, VFC-21, VFC-22, VFC-23, VFC-24, VFC-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC-37, VFC-38, VFC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC-48, VFC-49, VFC-50, VFC-51, VFC-52, VFC-53, VFC-54, VFC-55 , VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC-61, VFC-62, VFC-63, VFC-64, VFC-65, VFC-66, VFC-67 , VFC-68, VFC-69, VFC-70, VFC-71, VFC-72, VFC-73, VFC-74, VFC-75, VFC-76, VFC-77, VFC-78, VFC-7 9, VFC-80, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, VFC-87, VFC-88, VFC-89, or VFC-90.In some embodiments, linker region B is selected from the group consisting of VFC-1, VFC-2, VFC-3, VFC-4, VFC-5, VFC-6, VFC-7, VFC-8, VFC-9, VFC-10, VFC-11, VFC-12, VFC-13, VFC-14, VFC-15, VFC-16, VFC-17, VFC-18, VFC-19, VFC-20, VFC-21, VFC-22, VFC-23, VFC-24, VFC-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC-37, VFC-38, VFC-39, VFC-40, VFC-41, VFC- FC-20, VFC-21, VFC-22, VFC-23, VFC-24, VFC-25, VFC-26, VFC-27, VFC-28, VFC-29, VFC-30, VFC-31, VFC-32, VFC-33, VFC-34, VFC-35, VFC-36, VFC-37, VFC-38, VFC-39, VFC-40, VFC-41, VFC-42, VFC-43, VFC-44, VFC-45, VFC-46, VFC-47, VFC-48, VFC-49, VFC-50, VFC-51, VFC-52, VFC-53, VFC-54, VFC-55 , VFC-56, VFC-57, VFC-58, VFC-59, VFC-60, VFC-61, VFC-62, VFC-63, VFC-64, VFC-65, VFC-66, VFC-67 , VFC-68, VFC-69, VFC-70, VFC-71, VFC-72, VFC-73, VFC-74, VFC-75, VFC-76, VFC-77, VFC-78, VFC-7 9, VFC-80, VFC-81, VFC-82, VFC-83, VFC-84, VFC-85, VFC-86, VFC-87, VFC-88, VFC-89, or VFC-90.In some embodiments, linker region A is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56 6, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ...

Claims

1. 1. A variant IgG Fc polypeptide having at least 95% sequence identity to SEQ ID NO: 88, with the proviso that said variant IgG Fc polypeptide comprises a mutation or set of mutations at any one position or any combination of positions (according to EU numbering) selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330 compared to SEQ ID NO:

88.

2. 2. The variant IgG Fc polypeptide of claim 1, wherein the variant IgG Fc polypeptide comprises a mutation that enhances selective binding to FcγRIIβ over FcγRIIα.

3. the variant IgG Fc polypeptide Mutations at positions 237 and 238 compared to SEQ ID NO: 88; Mutations at positions 237, 238, 240, 269, 270, and 330 relative to SEQ ID NO: 88; Mutations at positions 234, 235, 329, 268, and 271 compared to SEQ ID NO: 88; Mutations at positions 238, 269, 270, and 330 compared to SEQ ID NO: 88; Mutations at positions 237, 238, 269, 270, and 330 compared to SEQ ID NO: 88; Mutations at positions 237, 238, 239, 269, 270, and 330 relative to SEQ ID NO: 88; Mutations at positions 235, 238, 269, 270, and 330 compared to SEQ ID NO: 88; mutations at positions 235, 238, 269, 270, and 330, and an insertion of the amino acid sequence GEV between positions 233 and 234, compared to SEQ ID NO: 88; Mutations at positions 238, 269, 270, and 330 compared to SEQ ID NO: 88; mutations at positions 234, 235, 239, 329, 268, and 271 relative to SEQ ID NO: 88; or mutations at positions 234 and 235 compared to SEQ ID NO: 88; or 2. The variant IgG Fc polypeptide of claim 1, comprising a set of mutations selected from any combination thereof.

4. 4. The variant IgG Fc polypeptide of any one of claims 1 to 3, wherein the variant IgG Fc polypeptide comprises one or more mutations selected from G237E, P238E, L234F, L235E, L235V, G237D, P238D, P238G, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof, compared to SEQ ID NO:

88.

5. the variant IgG Fc polypeptide A set of mutations G237E and P238E compared to SEQ ID NO: 88; a set of mutations compared to SEQ ID NO: 88: G237D, P238G, V240A, E269D, D270E, and A330R; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, P329A, H268D, and P271G; a set of mutations P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88; a set of mutations compared to SEQ ID NO: 88: G237D, P238G, E269D, D270E, and A330R; a set of mutations compared to SEQ ID NO: 88: G237D, P238S, S239G, E269D, D270E, and A330R; a set of mutations compared to SEQ ID NO: 88: L235V, P238E, E269D, D270E, and A330R; A set of mutations compared to SEQ ID NO: 88: L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234; a set of mutations compared to SEQ ID NO: 88: P238S, E269D, D270E, and A330R; a set of mutations compared to SEQ ID NO: 88: L234F, L235E, S239D, P329A, H268D, and P271G; a set of mutations L234F and L235E compared to SEQ ID NO: 88; or 2. The variant IgG Fc polypeptide of claim 1, comprising a set of mutations selected from any combination thereof.

6. 6. The variant IgG Fc polypeptide of any one of claims 1 to 5, wherein said variant IgG Fc polypeptide further comprises, in addition to said set of mutations, at least, about, or exactly 1-10, 1-20, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mutations compared to SEQ ID NO:

88.

7. The variant IgG Fc polypeptide is selected from the group consisting of SEQ ID NO:102, SEQ ID NO:40, SEQ ID NO:77, SEQ ID NO:103, SEQ ID NO:86, SEQ ID NO:104, SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:4 2. The variant IgG Fc polypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, or SEQ ID NO:

86.

8. The variant IgG Fc polypeptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49 , SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO:104, with the proviso that said variant IgG 2. The variant IgG Fc polypeptide of claim 1, provided that the Fc polypeptide comprises a mutation or set of mutations at any one position or any combination of positions selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330 relative to SEQ ID NO:

88.

9. The variant IgG Fc polypeptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49 , SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO:104, with the proviso that said variant IgG 2. The variant IgG Fc polypeptide of claim 1, wherein the Fc polypeptide comprises one or more mutations selected from L234F, L235E, L235V, G237D, G237E, P238D, P238G, P238E, P238S, S239G, S239D, V240A, H268D, E269D, D270E, P271G, P329A, A330R, an insertion of the amino acid sequence GEV between positions 233 and 234, and any combination thereof, compared to SEQ ID NO:

88.

10. 2. The variant IgG Fc polypeptide of claim 1, wherein the variant IgG Fc polypeptide associates with another variant IgG Fc polypeptide to form a dimeric molecule, which may be a heterodimer or a homodimer.

11. 8. The variant IgG Fc polypeptide of claim 7, wherein the variant IgG Fc polypeptide associates with another variant IgG Fc polypeptide to form a dimeric molecule, which may be a heterodimer or a homodimer.

12. the first polypeptide of the dimer is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO: SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO:104; the second polypeptide of the dimer is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO: SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO:104; 11. The variant IgG Fc polypeptide of claim 10, wherein the first polypeptide of the dimer and the second polypeptide of the dimer may be the same or different.

13. the dimer comprises a first polypeptide and a second polypeptide; the first polypeptide comprises the amino acid sequence of SEQ ID NO: 102 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 102; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 103 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 103; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 104 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 104; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:1 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:1; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:2 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:2; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:3 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:3; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:4 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:4; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:5 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:5; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:6 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:6; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:7 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:7; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:8 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:8; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:9 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:9; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 10 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 10; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 11 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 11; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 12 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 12; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 13; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 14 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 15 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 15; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 16 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 16; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 17 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 17; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 18 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 18; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 19 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 19; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:20 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:20; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:21 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:21; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:22 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:22; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:23 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:23; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:24 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:24; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:25 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:25; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:26 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:26; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:27 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:27; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:28 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:28; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:29 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:29; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 30 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 30; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:31 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:31; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 32 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 32; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 33 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 33; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 34 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 34; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:35 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:35; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 36 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 36; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:37 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:37; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 38 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 38; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:39 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:39; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 40 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 40; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:41 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:41; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:42 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:42; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:43 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:43; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:44 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:44; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:45 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:45; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:46 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:46; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:47 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:47; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:48 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:48; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:49 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:49; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:50 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:50; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:51 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:51; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:52 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:52; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:53 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:53; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:54 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:54; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:55 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:55; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:56 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:56; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:57 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:57; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:58 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:58; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:59 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:59; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:60 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:60; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:61 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:61; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:62 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:62; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:63 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:63; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:64 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:64; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:65 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:65; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:66 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:66; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:67 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:67; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:68 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:68; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:69 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:69; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 70 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 70; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:71 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:71; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:72 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:72; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:73 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:73; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:74 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:74; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:75 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:75; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:76 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:76; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:77 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:77; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:78 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:78; or the first polypeptide comprises the amino acid sequence of SEQ ID NO:79 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:79; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 80 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 80; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 81 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 81; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 82 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 82; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 83 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 83; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 84 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 84; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 85 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 85; or the first polypeptide comprises the amino acid sequence of SEQ ID NO: 86 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 86; or 11. The variant IgG Fc polypeptide of claim 10, wherein said first polypeptide comprises the amino acid sequence of SEQ ID NO:87 and said second polypeptide comprises the amino acid sequence of SEQ ID NO:

87.

14. A polypeptide comprising the Fc variant of any one of claims 1 to 3, 5, or 7 to 13 and an inhibitory receptor effector domain, wherein the inhibitory receptor effector domain is an antibody that binds to PD-1 or LAG-3.

15. 2. The polypeptide of claim 1, wherein the polypeptide has at least 95% identity to an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 88, provided that the polypeptide comprises a glutamic acid (E) residue at position 237 and a glutamic acid (E) residue at position 238, wherein the positions are according to EU numbering.

16. 2. The polypeptide of claim 1, wherein the polypeptide has at least 95% identity to an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the polypeptide comprises an aspartic acid (D) residue at position 237, a glycine residue at position 238, an alanine residue at position 240, an aspartic acid (D) residue at position 269, a glutamic acid (E) residue at position 270, and an arginine residue at position 330, wherein the positions are according to EU numbering.

17. 2. The polypeptide of claim 1, wherein the polypeptide has at least 95% identity to an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 88, with the proviso that the polypeptide comprises a phenylalanine residue at position 234, a glutamic acid residue at position 235, an aspartic acid residue at position 268, a glycine residue at position 271, and an alanine residue at position 329, wherein the positions are according to EU numbering.

18. 16. The polypeptide of claim 15, wherein the polypeptide has at least 95% identity with an amino acid sequence comprising the sequence of SEQ ID NO:

40.

19. 16. The polypeptide of claim 15, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:

40.

20. 16. The polypeptide of claim 15, wherein the polypeptide has at least 95% identity with an amino acid sequence comprising the sequence of SEQ ID NO:

102.

21. 16. The polypeptide of claim 15, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:

102.

22. 17. The polypeptide of claim 16, wherein the polypeptide has at least 95% identity with an amino acid sequence comprising the sequence of SEQ ID NO:

77.

23. 17. The polypeptide of claim 16, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:

77.

24. 17. The polypeptide of claim 16, wherein the polypeptide has at least 95% identity with an amino acid sequence comprising the sequence of SEQ ID NO:

103.

25. 17. The polypeptide of claim 16, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:

103.

26. 18. The polypeptide of claim 17, wherein the polypeptide has at least 95% identity with an amino acid sequence comprising the sequence of SEQ ID NO:

86.

27. 18. The polypeptide of claim 17, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:

86.

28. 18. The polypeptide of claim 17, wherein the polypeptide has at least 95% identity with an amino acid sequence comprising the sequence of SEQ ID NO:

104.

29. 18. The polypeptide of claim 17, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:

104.

30. 30. A composition comprising a homodimer comprising a first polypeptide and a second polypeptide, wherein the first polypeptide and the second polypeptide comprise the polypeptide of any one of claims 15 to 29, and the first polypeptide and the second polypeptide are the same.

31. 30. A composition comprising a heterodimer comprising a first polypeptide and a second polypeptide, wherein the first polypeptide and the second polypeptide each independently comprise a polypeptide according to any one of claims 15 to 29, and wherein the first polypeptide and the second polypeptide are different.

32. 30. The polypeptide of any one of claims 15 to 29, wherein the polypeptide is linked to an inhibitory receptor effector domain.

33. 33. The polypeptide of claim 32, wherein the inhibitory receptor effector domain is an antibody that binds to PD-1, LAG-3, or CTLA4.

34. The polypeptide of claim 33, wherein the antibody is an antibody that binds to PD-1.

35. The polypeptide of claim 34, wherein the antibody that binds to PD-1 is a PD-1 agonist.

36. A polypeptide comprising the polypeptide of claim 15 and an inhibitory receptor effector domain, wherein the inhibitory receptor effector domain is an antibody that binds to PD-1 or LAG-3.

37. A polypeptide comprising the polypeptide of claim 16 and an inhibitory receptor effector domain, wherein the inhibitory receptor effector domain is an antibody that binds to PD-1 or LAG-3.

38. A polypeptide comprising the polypeptide of claim 17 and an inhibitory receptor effector domain, wherein the inhibitory receptor effector domain is an antibody that binds to PD-1 or LAG-3.

39. A polypeptide comprising the polypeptide of claim 21 and an inhibitory receptor effector domain, wherein the inhibitory receptor effector domain is an antibody that binds to PD-1 or LAG-3.

40. A polypeptide comprising the polypeptide of claim 25 and an inhibitory receptor effector domain, wherein the inhibitory receptor effector domain is an antibody that binds to PD-1 or LAG-3.

41. A polypeptide comprising the polypeptide of claim 29 and an inhibitory receptor effector domain, wherein the inhibitory receptor effector domain is an antibody that binds to PD-1 or LAG-3.

42. A polypeptide comprising: a variant IgG Fc polypeptide having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 88, with the proviso that said variant IgG Fc polypeptide comprises a mutation or set of mutations at any one position or any combination of positions selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330 compared to SEQ ID NO: 88; an inhibitory receptor effector domain; and an FcγRII-binding effector domain.

43. 10. A pharmaceutical composition comprising a polypeptide or composition according to any one of the preceding claims and at least one pharmaceutically acceptable excipient.

44. 10. A method for treating an autoimmune disorder in a subject, comprising administering to the subject a polypeptide described in any one of claims 1, 2, 3, 5, 7-13, 15-29, or 36-42, or a pharmaceutical composition comprising the same.

45. The autoimmune disorder may be rheumatoid arthritis, lupus, lupus nephritis, drug-induced lupus, discoid lupus erythematosus, systemic lupus erythematosus (SLE), cutaneous lupus erythematosus, lupus vasculitis, Sjogren's syndrome, ulcerative colitis, Crohn's disease, diabetes mellitus type 1, idiopathic inflammatory myopathy, giant cell arteritis, myocarditis, post-myocardial infarction syndrome, post-pericardiotomy syndrome, subacute bacterial endocarditis, anti-glomerular basement membrane nephritis, interstitial cystitis, membranous glomerulonephropathy, chronic kidney disease (CKD), autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, antisynthetase syndrome, alopecia areata, autoimmune angioedema, autoimmune progesterone dermatitis, overlapping connective tissue disease syndrome, polymyalgia rheumatica, autoimmune urticaria, bullous idiopathic rheumatoid arthritis, or Pemphigus, cicatricial pemphigoid, dermatitis herpetiformis, epidermolysis bullosa acquisita, erythema nodosum, antineutrophil cytoplasmic antibody-associated vasculitis, Henoch-Schönlein purpura, Cogan's syndrome, Buerger's disease, Susan's disease, immune complex vasculitis, primary vasculitis of the CNS, pemphigoid of pregnancy, hidradenitis suppurativa, lichen planus, lichen sclerosus, linear IGA disease (LAD), localized scleroderma, pemphigus vulgaris, acute Pityriasis varioliformis, Mucker-Habermann disease, psoriasis, systemic sclerosis, vitiligo, Addison's disease, polyglandular autoimmune syndrome (APS) type 1, polyglandular autoimmune syndrome (APS) type 2, juvenile idiopathic arthritis, juvenile dermatomyositis, autoimmune encephalopathy, polyglandular autoimmune syndrome (APS) type 3, autoimmune pancreatitis (AIP), autoimmune thyroiditis, Ord's thyroiditis thyroiditis), Graves' disease, autoimmune oophoritis, endometriosis, autoimmune orchitis, Sjogren's syndrome, autoimmune enteropathy, celiac disease, microscopic colitis, thrombocytopenia, steatosis, dolorosa, adult-onset Still's disease, ankylosing spondylitis, CREST syndrome, enthesitis-associated arthritis, eosinophilic fasciitis, Felty's syndrome, IgG4-related disease, juvenile arthritis, Lyme disease (chronic), mixed connective tissue disease ( MCTD), relapsing rheumatoid arthritis, Parry-Romberg syndrome, Parsonage-Turner syndrome, psoriatic arthritis, IBD-related arthritis, reactive arthritis, relapsing polychondritis, retroperitoneal fibrosis, rheumatic fever, autoimmune complications of immune checkpoint inhibitors (IRAE), sarcoidosis, neurosarcoidosis, Schnitzler syndrome, undifferentiated connective tissue disease (UCTD), dermatomyositis, IgG4-related disease, fibromyalgia,Antiphospholipid syndrome, inclusion body myositis, myositis, myasthenia gravis, neuromyotonia, paraneoplastic cerebellar degeneration, polymyositis, acute disseminated encephalomyelitis (ADEM), adult-onset Still's disease, acute motor axonal neuropathy, anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis, warm antibody hemolytic anemia (wAIHA), immune thrombocytopenia, immune thrombocytopenia, thrombotic thrombocytopenia, pernicious anemia, aplastic anemia, Evan's syndrome, autoimmune neutropenia, acquired von Willebrand syndrome, habitual abortion, Rh incompatibility, Barrow concentric sclerosis, Bickerstaff encephalitis inflammation, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, Hashimoto's encephalopathy, idiopathic inflammatory demyelinating diseases, Lambert-Eaton myasthenic syndrome, primary biliary sclerosis, glomerulonephritis, glomerular basement membrane disease, multiple sclerosis, Oshtoran syndrome, Streptococcus-associated childhood autoimmune neuropsychiatric disorders (PANDAS), progressive inflammatory neuropathy, restless legs syndrome, pemphigus foliaceus including Brazilian pemphigus, transplantation, antibody-mediated rejection, alloantibody hypersensitivity, xenoantibody-mediated rejection, solid organ rejection, acute graft-versus-host disease and Chronic, stiff-person syndrome, Sydenham's chorea, transverse myelitis, autoimmune retinopathy, autoimmune uveitis, uveitis, Cogan's syndrome, Graves' ophthalmopathy, amyotrophic lateral sclerosis (ALS), Parkinson's disease, autoimmune encephalitis, CNS vasculitis, chronic idiopathic demyelinating polyneuropathy (CIDP), keratitis, intermediate uveitis, lignine conjunctivitis, Mooren's ulcer, neuromyelitis optica, opsoclonus-myoclonus syndrome, optic neuritis, scleritis, Susac syndrome, sympathetic ophthalmia, Trosser-Hunt syndrome, rheumatic heart disease, chronic sinusitis with nasal polyps, allergic bronchopulmonary (bronchoplumonary) fungal infections, hypersensitivity pneumonitis, rheumatoid arthritis-related interstitial lung disease (RA-ILD), nonspecific interstitial pneumonia, allergic asthma, infectious diseases / vaccinations, antibody-dependent enhancement (similar to dengue virus infection), chronic meningitis, anti-myelin oligodendrocyte glycoprotein (MOG) disease, activated DLBCL, anti-drug antibodies, anti-gene therapy vector antibodies (anti-AAV antibodies), antibodies against therapeutic biological agents (cytokines, monoclonal antibodies, enzymes, coagulation factors), autoimmune inner ear disease (AIED), Meniere's disease, Behcet's disease,Eosinophilic granulomatosis with polyangiitis (EGPA), polyglandular autoimmune endocrine syndrome, granulomatosis with polyangiitis (GPA), IgA vasculitis (IgAV), Kawasaki disease, leukocytoclastic vasculitis, rheumatoid vasculitis, microscopic polyangiitis (MPA), polyarteritis nodosa (PAN), polymyalgia rheumatica, vasculitis, primary immunodeficiency, pyoderma gangrenosum, agammaglobulinemia, amyloidosis, amyotrophic lateral sclerosis, antitubular basement membrane nephritis, atopic allergy, atopic dermatitis, autoimmune peripheral neuropathy, Blau syndrome, Castleman disease, Chagas disease, chronic obstructive pulmonary disease 45. The method of claim 44, wherein the disease is selected from chronic relapsing multifocal osteomyelitis, complement component 2 deficiency, contact dermatitis, Cushing's syndrome, cutaneous leukocytoclastic vasculitis, Dego disease, eczema, eosinophilic gastroenteritis, eosinophilic pneumonia, erythroblastosis fetalis, fibrodysplasia ossificans progressiva, gastrointestinal pemphigoid, hypogammaglobulinemia, idiopathic giant cell myocarditis, idiopathic pulmonary fibrosis, IgA nephropathy, immunoregulatory lipoproteins, IPEX syndrome, lignified conjunctivitis, Majeed syndrome, narcolepsy, Rasmussen's encephalitis, schizophrenia, serum sickness, spondyloathropathy, Sweet's syndrome, Takayasu's arteritis, or any combination thereof.

46. A method for treating cancer in a subject, comprising administering to said subject a polypeptide or composition according to any one of claims 1 to 42, or a pharmaceutical composition or method comprising the same.

47. 47. The method of claim 46, wherein the cancer is a solid or liquid tumor, including but not limited to hematopoietic cancer, lymphatic system cancer, skin cancer, head and neck cancer, genitourinary cancer, blood cancer, lung cancer, breast cancer, brain cancer, esophageal cancer, colorectal cancer, or pancreatic cancer.

48. A method for regulating a cellular interaction between a first cell and a second cell in a subject using a polypeptide, the method comprising administering to the subject comprising the cell a polypeptide described in any one of claims 1, 2, 3, 5, 7-13, 15-29, or 36-42, or a pharmaceutical composition comprising the same.

49. 49. The method of claim 48, wherein the first cell is a T cell, an NK cell, or a dendritic cell, and the second cell is a B cell, an antigen-presenting cell (APC), or a myeloid cell.

50. 42. A method for inhibiting activated immune cells in contact with B cells, antigen-presenting cells (APCs), or myeloid cells, comprising contacting said cells or a subject containing said cells with a polypeptide or composition according to any one of claims 1, 2, 3, 5, 7-13, 15-29, or 36-42, or a pharmaceutical composition comprising the same.

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