Variant IgG FC polypeptides and uses thereof

Abstract

Embodiments provided herein provide variant IgG Fc polypeptides, dimer molecules, pharmaceutical compositions, and methods that can be used to target a cell to modulate the activity of the cell to treat a disorder, such as an autoimmune disorder or cancer.

Description

[0001] Cross Reference to Related Applications

[0002] 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 hereby incorporated by reference in its entirety.

[0003] Reference to Sequence Listing Submitted Electronically

[0004] The instant application contains a Sequence Listing which has been submitted electronically in XML format and which is hereby incorporated 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. TECHNICAL FIELD

[0005] Provided herein are embodiments relating to compositions that target cells to modulate an immune response. BACKGROUND

[0006] FcγRIIβ is the only FcγR expressed on cells (Smith, K.G.C. and Clatworthy, M.R., Nat Rev Immunol. May 2010; 10(5):328-343). It has been reported that the interaction of the Fc region of an antibody with FcγRIIβ inhibits the primary immune response of B cells (Smith, K.G.C. and Clatworthy, M.R., Nat Rev Immunol. May 2010; 10(5):328-343). In addition, it has been reported that when FcγRIIβ on B cells and the B cell receptor (BCR) are cross-linked via immune complexes in the blood, B cell activation is inhibited and antibody production by B cells is inhibited. IgG1, which is known to be used primarily as a therapeutic antibody on the market, is known to bind not only to FcγRIIβ but also to activate FcγRs strongly. By utilizing an Fc region that has enhanced FcγRIIβ binding or improved FcγRIIβ binding selectivity compared to an activating FcγR, it is possible to develop a therapeutic antibody that has greater immunosuppressive properties compared to the immunosuppressive properties of IgG1. Therefore, an antibody having an Fc with improved FcγRIIβ binding activity is suggested to be promising as a therapeutic agent for inflammatory diseases such as autoimmune diseases. The embodiments provided herein meet these needs and others. SUMMARY

[0007] In some embodiments, a variant IgG Fc polypeptide that selectively binds to FcyRIIb but not FcyRIIa is provided, wherein the variant IgG Fc polypeptide comprises a mutation selected from the 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, 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, VFC-87, VFC-88, VFC-89, or VFC-90.

[0008] In some embodiments, a polypeptide is provided that comprises a variant IgG Fc polypeptide that selectively binds to FcyRIIb but not FcyRIIa, wherein the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to 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: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NONO: 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 an inhibitory receptor effector domain.

[0009] In some embodiments, a polypeptide is provided that comprises a variant IgG Fc polypeptide that selectively binds to FcyRIIb but not FcyRIIa, wherein the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to 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: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NONO: 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; an inhibitory receptor effector domain; and an FcyRII binding effector domain.

[0010] In some embodiments, a method of treating an autoimmune disorder in a subject is provided, wherein the method comprises 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 the same.

[0011] In some embodiments, a method of treating a cancer in a subject is provided, wherein the method comprises 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 the same.

[0012] In some embodiments, a method of modulating the interaction of at least two different types of cells is provided, wherein the method comprises 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 the same.

[0013] In some embodiments, a method of inhibiting an activated immune cell in contact with a B cell, an antigen presenting cell (APC), or a myeloid cell is provided, wherein the method comprises 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 the same.

[0014] In some embodiments, a method of activating or enhancing the behavior of an activated immune cell in contact with a B cell, an antigen presenting cell (APC), or a myeloid cell is provided, wherein the method comprises 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 the same. BRIEF DESCRIPTION OF DRAWINGS

[0015] Figures 1A-1Care bar graphs showing IL-2 (A), IFNg (B), and TNFa (C) production levels following treatment with VFC-IR agonists or control molecules.

[0016] Figures 2A-2C Binding affinities of various articles were exemplified.

[0017] Figure 3 TNF-a production in response to various articles was exemplified.

[0018] Figure 4 Granzyme B and IFN-g production in response to various articles was exemplified.

[0019] Figures 5A-5B ADCC induction in response to various articles was exemplified.

[0020] Figure 6 C1q binding to various articles was exemplified. DETAILED DESCRIPTION

[0021] 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 herein by reference in its entirety.

[0022] As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise.

[0023] As used herein, the term “about” means that a value is approximate and that minor variations do not significantly impact the practice of the disclosed embodiments. When a numerical limitation is used, “about” means that the value can vary by ±5% unless the context indicates otherwise. Thus, about 100 means 95 to 105.

[0024] 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.

[0025] As used herein, the term "contacting" means bringing together two elements 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, for example, introducing the compound into a sample containing a cell preparation or purified preparation containing a target.

[0026] As used herein, the term "comprising" (as well as any form of comprising, such as "comprise," "comprises," and "comprised"), "having" (as well as any form of having, such as "have" and "has"), "including" (as well as any form of including, such as "includes" and "include"), or "containing" (as well as any form of containing, such as "contains" and "contain") is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. Any composition or method reciting "comprising" is also to be understood as describing compositions or methods that are composed of or consisting essentially of the recited components or elements, in addition to any additional components or elements.

[0027] As used herein, when the term "fused" or "linked" is used to refer to proteins or molecules having different domains or heterologous sequences, it means that the protein domains are part of the same peptide chain, which are linked to each other by peptide bonds or other covalent bonds. The domains or moieties can be linked or fused to each other directly, or another domain or peptide sequence can be interposed between two domains or sequences, and such sequences are still considered to be fused or linked to each other.

[0028] As used herein, the terms "individual," "subject," or "patient," which are used interchangeably, mean any animal, including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, swine; cattle, sheep, horses, or primates, such as humans.

[0029] As used herein, the term "inhibiting" means reducing the result, symptom, or activity as compared to the activity or result in the absence of the compound that inhibits 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%. The result, symptom, or activity can also be inhibited if it is completely eliminated or abolished.

[0030] As used herein, the phrase "in need thereof means that a subject has been identified as requiring a particular method or treatment. In some embodiments, the identification can be made by any diagnostic means. In any of the methods and treatments described herein, a subject can be in need thereof. In some embodiments, a subject is in an environment in which a particular disease, disorder, or condition is prevalent or is about to travel to such an environment.

[0031] As used herein, the phrase "an integer from X to Y" means any integer including the endpoints. For example, the phrase "an integer from 1 to 5" means 1, 2, 3, 4, or 5.

[0032] As used herein, the phrase "ophthalmically acceptable" means that there are no persistent deleterious effects on the eye being treated or its function, or on the general health of the subject receiving treatment. It is recognized, however, that there can be transient effects such as mild irritation or a "stinging" sensation upon topical ocular administration of a drug, and the presence of such transient effects is not inconsistent with a composition, formulation, or ingredient (e.g., excipient) as discussed herein being "ophthalmically acceptable." In some embodiments, a pharmaceutical composition can be ophthalmically acceptable or suitable for ophthalmic administration.

[0033] 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.

[0034] "Specifically binds" or "binds specifically to" or "is specific for" a particular antigen, target, or epitope means binding that is measurable above non-specific interaction. For example, specific binding can be measured by determining binding of a molecule compared to binding of a control molecule, which is typically a similarly structured molecule 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.

[0035] Specific binding to a particular antigen, target, or epitope can be exhibited, for example, by an antibody that has 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 greater K D , where K Dis the off-rate of a particular antibody-target interaction. Typically, an antibody that specifically binds an antigen or target has a Kd that is or is at least 2, 4, 5, 10, 20, 50, 100, 500, 1000, 5,000, 10,000 or more times greater for a control molecule relative to the antigen or epitope D .

[0036] In some embodiments, specific binding to a particular antigen, target or epitope can be exhibited, for example, by an antibody that has a Kd that is or is at least 2, 4, 5, 20, 50, 100, 500, 1000, 5,000, 10,000 or more times greater for the target, antigen or epitope relative to the target, antigen or epitope of a control A or Kd a where Kd A or Kd a is the on-rate of a particular antibody-antigen interaction.

[0037] As provided herein, the compounds and compositions provided herein can be used in the methods of treatment as provided herein. As used herein, the term "treat," "treated," or "treating" means both therapeutic treatment and prophylactic or preventative measures, wherein the object is to slow (lessen) an undesired physiological condition, disorder or disease, or to enhance or improve a desirable clinical outcome. For purposes of this embodiment, beneficial or desired clinical results include, but are not limited to, abatement; lessening of symptoms; diminishment of extent of condition, disorder or disease; stabilized (i.e., not worsening) state of condition, disorder or disease; delay in onset or slowing of condition, disorder or disease progression; amelioration of the condition, disorder or disease state, whether partial or total, whether detectable or undetectable; improvement(s) in at least one measurable physical parameter, but not necessarily discernible by the subject; or enhancement of the prognosis, of the condition, disorder or disease. Treatment includes eliciting a clinically significant response without intolerable side effects. Treatment also includes prolonging survival as compared to expected survival if not receiving treatment, as applicable to the particular disease. Thus, "treatment of an autoimmune condition" or "treating autoimmunity" means alleviating or ameliorating any of the major phenomena or secondary symptoms associated with such conditions when the terms "treat," "treated," or "treating" are used in conjunction with an autoimmune condition or other condition described herein.

[0038] As used herein, the terms "variant," "molecule," "therapeutic agent," "therapeutic compound," "compound," "polypeptide," or "protein" can be used interchangeably and relate to the variants, molecules, therapeutic agents, therapeutic compounds, compounds, polypeptides, and proteins disclosed herein.

[0039] Variant Fc molecules

[0040] As used herein, “isotype” refers to an immunoglobulin class (e.g., IgGl, IgG2, IgG3, IgG4, IgM, IgAl, 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., CHI domain, hinge, CH2 domain, and CH3 domain) is catalogued in the UniProt database, available online, as, e.g., P01857 (IgGl), P01859 (IgG2), P01860 (IgG3), and P01861 (IgG4), or different allotypes thereof (SEQ ID NOs: 1, 2, 3, and 4, respectively). As used herein, a domain (e.g., hinge) of a heavy chain constant region belongs to an “IgGl isotype,” “IgG2 isotype,” “IgG3 isotype,” or “IgG4 isotype” if it comprises the amino acid sequence of the corresponding domain of the respective isotype or a variant thereof (with a higher homology to the corresponding domain of the respective isotype than to the corresponding domains of the other isotypes).

[0041] As used herein, “variant Fc polypeptide” and “variant IgG Fc polypeptide” refer to the same Fc polypeptide comprising at least one mutation relative to the wild-type isotype amino acid sequence, and thus, the terms “variant Fc polypeptide” and “variant IgG Fc polypeptide” can be used interchangeably.

[0042] “allotype” refers to naturally occurring variants within a specific isotype group that differ by a few amino acids (see, e.g., Jefferies et al. (2009) mAbs 1:1). The molecules described herein can belong to any allotype.

[0043] A “wild-type” protein or portion thereof is a form of a protein as found in nature. The amino acid sequence of a wild-type protein (e.g., heavy chain constant region) is that of a protein as found in nature. There can be more than one amino acid sequence of a wild-type protein due to allotype differences. For example, there are several allotypes of naturally occurring human IGg1 heavy chain constant regions (e.g., Jeffries et al. (2009) mAbs 1:1).

[0044] The immunoglobulin can be from any of the commonly known isotypes, including but not limited to IgA, secretory IgA, IgG, and IgM. IgG isotypes are divided into subclasses in certain species: IgGl, IgG2, IgG3, and IgG4 in humans, and IgGl, IgG2a, IgG2b, and IgG3 in mice. In certain embodiments, the antibodies described herein are of the human IgGl or IgG2 subtype. Immunoglobulins, such as human IgGl, exist in several allotypes, which differ from each other by at most a few amino acids.

[0045] In certain embodiments, the IgG protein (underlined hinge region) is as provided in Table 1.

[0046]

[0047] The "Fc region" (fragment, crystallizable region) or "Fc domain" or "Fc" refers to the C-terminal region of the antibody heavy chain that mediates the binding of an immunoglobulin to host tissues or factors including binding to Fc receptors located on various cells of the immune system (e.g., effector cells) or to the first component (Clq) of the classical complement system. Thus, the Fc region of an antibody of the isotype IgG comprises the constant region of the heavy chain of the antibody excluding the first constant region immunoglobulin domain (CHI). In the IgG, IgA, and IgD antibody isotypes, the Fc region comprises the CH2 and CH3 constant regions of each of the two heavy chains of the antibody; the IgM and IgE Fc regions comprise three heavy chain constant domains (CH domains 2-4) in each polypeptide chain. For IgG, the Fc region comprises the immunoglobulin domains consisting of hinge, CH2 and CH3. For the purposes herein, the Fc region is defined as starting 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 US Patent Application Publication No. 2008 / 0248028. Figure 3 c to Figure 3f, These documents can be referred to as EU numbers. In some embodiments, the Fc region comprises a hinge region. The Fc can be a native (or naturally occurring or wild type) Fc, including any allotype variant or variant Fc (e.g., a non-naturally occurring Fc) comprising, e.g., 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 can 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. A modified or mutated Fc can have enhanced or reduced effector function and / or half-life. Fc can refer to the region, alone or in the context of a protein polypeptide comprising an Fc, such as a “binding protein comprising an Fc region,” also referred to as an “Fc fusion protein” (e.g., an antibody or immunoadhesin), in the context of that region. In some embodiments, a modified or variant Fc molecule has enhanced binding to FcyRIIb.

[0048] “Hinge,” “hinge domain,” or “hinge region,” or “antibody hinge region,” refers to the domain of a heavy chain constant region that joins 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 degrees 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 as well as variants thereof (e.g., a non-naturally occurring hinge or a modified hinge). For example, the term “IgG1 hinge” includes a wild type IgG1 hinge, as 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.

[0049]

[0050] The term “CH1 domain” refers to the heavy chain constant region that connects the variable domain to the hinge in the heavy chain constant domain. As used herein, the CH1 domain includes wild type CH1 domains as well as variants thereof (e.g., a non-naturally occurring CH1 domain or a modified CH1 domain). As used herein, the CH1 domain includes amino acid residues 1-98 of IgG1; amino acid residues 1-98 of IgG2; amino acid residues 1-98 of IgG3; and amino acid residues 1-98 of IgG4. For example, the term “CH1 domain” includes a wild type CH1 domain, as well as variants thereof 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).

[0051] The term“CH2 domain” refers to the heavy chain constant region in the heavy chain constant domain that connects the hinge to the CH3 domain. As used herein, the CH2 domain includes wild-type CH2 domains as well as variants thereof (e.g., non-naturally occurring CH2 domains or modified CH2 domains). As used herein, the CH2 domain includes amino acid residues 111 to 223 of IgG1; amino acid residues 111-219 of IgG2; amino acid residues 161-270 of IgG3; and amino acid residues 111-220 of IgG4. For example, the term“CH2 domain” includes wild-type CH2 domains as well as variants thereof 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).

[0052] The term“CH3 domain” refers to the heavy chain constant region in the heavy chain constant domain that is C-terminal to the CH2 domain. As used herein, the CH3 domain includes wild-type CH3 domains as well as variants thereof (e.g., non-naturally occurring CH3 domains or modified CH3 domains). As used herein, the CH3 domain includes amino acid residues 224-330 of IgG1; amino acid residues 220-326 of IgG2; amino acid residues 271-376 of IgG3; and amino acid residues 226-322 of IgG4. For example, the term“CH3 domain” includes wild-type CH3 domains as well as variants thereof 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).

[0053] In some embodiments, the hinge / CH2 domain has an amino acid sequence such as provided in Table 3.

[0054]

[0055] Without being bound by a particular theory, mutating or isotype swapping the entire hinge region or CH2 region, or certain portions of the hinge region or CH2 region, in IgG1 results in a modified IgG1 that has enhanced or altered properties relative to IgG1 having a wild-type IgG1 constant region. For example, the IgG1 can have residues 111-223 replaced with residues 111-220 of IgG4. Other non-limiting examples include IgG1 having 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.

[0056] 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 can comprise a CH2 or CH3 region from one or more other isotypes. For example, the variant Fc can be an IgGl / IgG4 Fc molecule.

[0057] In some embodiments, the variant Fc comprises a CH2 region exchanged from another IgG isotype. Examples of CH2 regions include, but are not limited to:

[0058] SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

[0059] TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA (IgGl CH2, SEQ ID NO:

[0060] 100); or

[0061] SVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS

[0062] TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKA (IgG4 CH2, SEQ ID NO:

[0063] 101).

[0064] Provided herein are variant Fc molecules comprising a variant Fc domain. Exemplary variant Fc molecules comprising a variant Fc domain include an IgGl hinge, a CHI domain, a CH2 domain, and a CH3 domain, wherein at least one amino acid residue is mutated, wherein the mutation is a substitution, an insertion, or a deletion. In some embodiments, the insertion can be 1-5 residues. In some embodiments, the variant Fc molecule comprises an IgGl hinge and an IgG4 CH2 domain. In some embodiments, the variant Fc molecule comprises a mutated IgGl hinge and an IgG4 CH2 domain. The variant Fc molecule can have effector function similar to that of wild-type IgG, or can be engineered to have enhanced effector function relative to that of wild-type IgG. In some embodiments, the variant Fc molecule can have FcyRIIb binding affinity similar to that of wild-type IgG. In some embodiments, the variant Fc molecule can have FcyRIIb binding affinity enhanced relative to that of wild-type IgG. The variant Fc molecule can comprise a wild-type CHI, hinge, CH2, and / or CH3 domain or a variant thereof, e.g., a CHI, hinge, CH2, and / or CH3 domain having one or more amino acid substitutions, deletions, or additions relative 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.

[0065] In some embodiments, the variant Fc molecule comprises mutations that confer selective binding to FcyRIIb but not FcyRIIa. As used herein, the term “selective binding” with respect to FcyRIIb means that the Fc domain preferentially binds to FcyRIIb but not FcyRIIa, that is, has a higher affinity for FcyRIIb but not FcyRIIa. Examples of such mutations are provided in, e.g., US 7662926, US 7655229, US 2009 / 0087428, US 10919952, US 2007 / 0253948, and US 2006 / 0073142, each of which is hereby incorporated by reference in its entirety, including the particular mutations described as affecting FcyRIIb binding. In some embodiments, the mutations are as described in Shields et al., J. Biol. Chem. 2001, 276: 6591-6604, which is hereby incorporated by reference in its entirety.

[0066] In some embodiments, the Fc mutations are as described in U.S. Patent No. 10,618,965; EP Sequence No. 2679681; EP Sequence No. 3604330, US2014 / 0093496, US2015 / 0203577, U.S. Patent No. 9,540,451, EP Sequence No. 2331578; EP Sequence No. 3190128; U.S. Patent No. 9,902,773; EP Sequence No. 3342782, U.S. Publication No. 2020 / 0332024; EP Sequence No. 2796469; EP Sequence No. 2331578; EP Sequence No. 3190128; U.S. Patent No. 9,902,773, EP Sequence No. 2331578; EP Sequence No. 3190128, U.S. Patent No. 9,493,578, U.S. Patent No. 9,394,366, U.S. Patent No. 9,914,778, EP Sequence No. 2940043, US 9,890,218, EP Sequence No. 2940135; U.S. Patent No. 10,766,960, U.S. Patent No. 10,919,953, EP 3721900, EP 2889377, US2016 / 0039912, EP 2982689, or EP 3783017, each of which is hereby incorporated by reference in its entirety, including the particular mutations described that affect FcyRIIb or FcyRIIa binding.

[0067] In some embodiments, the Fc polypeptide comprises a mutation, a plurality of mutations, or a set of mutations that increase selectivity for FcyRIIb. In some embodiments, the Fc polypeptide comprises a mutation, a plurality of mutations, or a set of mutations that increase affinity for FcyRIIb. In some embodiments, the Fc polypeptide comprises a mutation, a plurality of mutations, or a set of mutations that increase selectivity and affinity for FcyRIIb. In some embodiments, the Fc polypeptide comprises a mutation, a plurality of mutations, or a set of mutations that increase selectivity for FcyRIIb but not FcyRIIa. In some embodiments, the Fc polypeptide comprises a mutation, a plurality of mutations, or a set of mutations that increase affinity for FcyRIIb but not FcyRIIa. In some embodiments, the Fc polypeptide comprises a mutation, a plurality of mutations, or a set of mutations that increase selectivity and affinity for FcyRIIb but not FcyRIIa. In some embodiments, the mutation, plurality of mutations, or set of mutations is a mutation, plurality of mutations, or set of mutations such as described herein.

[0068] 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, a deletion, or a 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, and wherein the mutation is an insertion, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228 and 234, according to SEQ ID NO:88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228 and 235, according to SEQ ID NO:88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 234 and 235, according to SEQ ID NO:88.

[0069] 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:88, wherein the mutation is an insertion, a deletion, or a 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, a deletion, or a 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, a deletion, or a 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, and wherein the mutation is an insertion, a deletion, or a 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, a deletion, or a 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, a deletion, or a 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, and wherein the mutation is an insertion, a deletion, or a 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, a deletion, or a 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, and wherein the mutation is an insertion, a deletion, or a substitution.In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 237, 238, or any combination thereof, wherein the mutation is an insertion, a deletion, or a substitution, according to SEQ ID NO: 88.

[0070] 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, a deletion, or a 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, and wherein the mutation is an insertion, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P228 and L234, according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 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.

[0071] 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, 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, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 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, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 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, a deletion, or a 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, a deletion, or a 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, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P228, L235, H268, K274, Y296, A327, A330, P331, or any combination thereof, according to SEQ ID NO: 88, wherein the mutation is an insertion, a deletion, or a substitution. 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, a deletion, or a 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, a deletion, or a 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, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P228, L234, L235, H268, K274, Y296, A330, P331, or any combination thereof, according to SEQ ID NO: 88, wherein the mutation is an insertion, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P228, H268, K274, Y296, A330, P331, or any combination thereof, according to SEQ ID NO: 88, wherein the mutation is an insertion, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P228, L234, H268, K274, Y296, A330, P331, or any combination thereof, according to SEQ ID NO: 88, wherein the mutation is an insertion, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position P228, L235, H268, K274, Y296, A330, P331, or any combination thereof, according to SEQ ID NO: 88, wherein the mutation is an insertion, a deletion, or a substitution. 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, a deletion, or a 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, a deletion, or a 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, a deletion, or a 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, a deletion, or a substitution.

[0072] In some embodiments, the variant Fc domain comprises mutations corresponding to mutations of 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 mutations of 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 mutations corresponding to a mutation at position L235E, according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions S228P and L234F, according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions S228P and L235E, according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions L234F and L235E, according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations of 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 mutations of 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 mutations of 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 mutations of 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 mutations of 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 mutations of 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 mutations of S228P, L234F, L235E, H268Q, K274Q, Y296F, A330S, P331S, or any combination thereof, according to SEQ ID NO: 88. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations of 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 mutations of 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 mutations of 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 mutations of 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 mutations of 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 mutations of L234F, H268Q, K274Q, Y296F, A327G, A330S, P331S, or any combination thereof, according to SEQ ID NO: 88.

[0073] In some embodiments, the variant IgG2 Fc domain comprises mutations corresponding to mutations at positions 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, or any combination thereof, according to SEQ ID NO: 89, and wherein the mutation is an insertion, a deletion, or a 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 a mutation at position 231, according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a mutation at position 232, according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a mutation at position 233, according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a mutation at position 234, according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a mutation at position 235, according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a mutation at position 236, according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a mutation at position 237, according to SEQ ID NO: 89. In some embodiments, the variant IgG2 Fc domain comprises a mutation corresponding to a 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, and wherein the mutation is an insertion, a deletion, or a substitution. 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.

[0074] In some embodiments, the variant IgG3 Fc domain comprises mutations corresponding to mutations 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: 90, and wherein the mutation is an insertion, a deletion, or a 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 a mutation at position 229, according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a mutation at position 230, according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a mutation at position 231, according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a mutation at position 232, according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a mutation at position 233, according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a mutation at position 234, according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a mutation at position 235, according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a mutation at position 236, according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a mutation at position 237, according to SEQ ID NO: 90. In some embodiments, the variant IgG3 Fc domain comprises a mutation corresponding to a 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, and wherein the mutation is an insertion, a deletion, or a substitution.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.

[0075] 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, a deletion, or a 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 a mutation at position 229, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 230, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 231, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 232, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 233, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 234, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 235, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 236, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 237, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 238, according to SEQ ID NO: 91. 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: 91, and wherein the mutation is an insertion, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 228 and 234, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 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.

[0076] 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, a deletion, or a 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, a deletion, or a 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, a deletion, or a 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, and wherein the mutation is an insertion, a deletion, or a 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, a deletion, or a 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, a deletion, or a 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: 91, and wherein the mutation is an insertion, a deletion, or a 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, a deletion, or a 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, and wherein the mutation is an insertion, a deletion, or a substitution.In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 237, 238, or any combination thereof, wherein the mutation is an insertion, a deletion, or a substitution, according to SEQ ID NO: 91.

[0077] 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, a deletion, or a 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, and wherein the mutation is an insertion, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position S228 and F234, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 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.

[0078] 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, 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, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 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, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position 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, a deletion, or a 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, a deletion, or a 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, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position S228, L235, Q268, Q274, F296, G327, S330, S331, or any combination thereof, according to SEQ ID NO: 91, wherein the mutation is an insertion, a deletion, or a substitution. 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, a deletion, or a 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, a deletion, or a 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, a deletion, or a 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, a deletion, or a 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, a deletion, or a 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, a deletion, or a substitution. In some embodiments, the variant Fc domain comprises a mutation corresponding to a mutation at position S228, L235, Q268, Q274, F296, S330, S331, or any combination thereof, according to SEQ ID NO: 91, wherein the mutation is an insertion, a deletion, or a 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, a deletion, or a 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, a deletion, or a 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, a deletion, or a 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, a deletion, or a substitution.

[0079] In some embodiments, the variant Fc domain comprises mutations corresponding to mutations of S228P, F234L, L235E, Q268H, Q274K, F296Y, 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 mutations of 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 mutations at position S228P, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at position F234L, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at position L235E, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions S228P and F234L, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions S228P and L235E, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations at positions F234L and L235E, according to SEQ ID NO: 91. In some embodiments, the variant Fc domain comprises mutations corresponding to mutations of 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 mutations of 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 mutations of 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 mutations of 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 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 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 F234L, Q268H, Q274K, F296Y, S330A, S331P, or any combination thereof, according to SEQ ID NO: 91.

[0080] 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.

[0081] 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, the substitution of the variant Fc polypeptide replaces the CH2 region of an IgG isotype with the CH2 region of a different IgG isotype. In some embodiments, the variant Fc polypeptide comprises a CH2 domain amino acid sequence that is at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identical 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 that is at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identical to SEQ ID NO: 96. In some embodiments, the variant Fc polypeptide comprises a CH2 domain amino acid sequence that is 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, the variant Fc polypeptide comprises a CH2 domain amino acid sequence that is 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, the variant Fc polypeptide comprises a CH2 domain amino acid sequence that is 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, the variant Fc polypeptide comprises a CH2 domain amino acid sequence that is 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 that is at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identical to SEQ ID NO: 101.

[0082] In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa.In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa.

[0083] In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 to FcyRIIb but not FcyRIIa.In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 to FcyRIIb but not FcyRIIa.In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 as compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 as compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 L234F as compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 L235E as compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa.In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 of S228P and L234F compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 of S228P and L235E compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa. In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 of L234F and L235E compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa.In some embodiments, the variant Fc polypeptide comprises a sequence that is 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% identical 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 of S228P, L234F, and L235E compared to SEQ ID NO: 88, and wherein the Fc polypeptide selectively binds to FcyRIIb but not FcyRIIa.

[0084] In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations that confer selective binding to FcyRIIb but not FcyRIIa. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations that enhance selective binding to FcyRIIb but not FcyRIIa. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the 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 the mutations associated with any one of VFC-1 to VFC-87 as provided in Table 4, and does not comprise a C-terminal lysine (K).

[0085]

[0086]

[0087]

[0088]

[0089]

[0090]

[0091]

[0092]

[0093]

[0094]

[0095] In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the 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, 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, VFC-87, VFC-88, VFC-89, VFC-90, or any combination thereof.In some embodiments, a variant IgG Fc polypeptide comprising one or more mutations of a mutation selected from 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, 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, VFC-87, VFC-88, VFC-89, VFC-90, or any combination thereof, has increased binding affinity to FcyRIIb over FcyRIIa.

[0096] In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-1. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-2. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-3. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-4. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-5. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-6. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-7. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-8. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-8. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-9. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-10. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-11. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-12. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-13. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-14. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the 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 the mutations associated with VFC-35. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-36. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-37. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-38. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-39. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-40. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-41. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-42. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-43. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-44. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-45. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-46. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-47. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-48. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the mutations associated with VFC-49. In some embodiments, the variant IgG Fc polypeptide comprises one or more mutations selected from the 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 the mutations associated with VFC-90.

[0097] In some embodiments, the mutation is a substitution, insertion, or deletion. In some embodiments, the insertion can be 1-5 residues or more.

[0098] In some embodiments, the variant IgG Fc polypeptide comprises a mutation at one or more positions (according to EU numbering) selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330, and any combination thereof, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 233, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 234, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 235, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 237, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 238, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 239, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 240, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 268, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 269, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 270, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 271, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 329, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at position 330, as compared to SEQ ID NO: 88.

[0099] In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the positions selected from 238, 269, 270, or 330 compared 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 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the positions selected from 237, 238, 269, 270, or 330 compared 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 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the 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 a 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 a mutation at any one or more of the 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 a 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 a mutation at any one or more of the positions selected from 235, 238, 269, 270, or 330 compared 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 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the 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 a 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 a mutation at any one or more of the positions selected from 235, 238, 269, 270, or 330 compared to SEQ ID NO: 88, and an insertion between positions 233 and 234.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, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the positions selected from 234, 235, 268, 271, or 329, as compared 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, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the positions selected from 234, 235, 239, 268, 271, or 329, as compared 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, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the positions selected from 234 or 235, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 234 and 235, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 237 and 238, as compared to SEQ ID NO: 88.

[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 one or more mutations selected from the 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, 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, VFC-87, VFC-88, VFC-89, or VFC-90. Non-limiting examples include a variant IgG Fc polypeptide 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 one or more mutations selected from the 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, 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, VFC-87, VFC-88, VFC-89, or VFC-90,wherein the variant IgG Fc polypeptide comprises one or more mutations selected from 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, 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, VFC-87, VFC-88, VFC-89, or VFC-90,以及氨基酸序列中不是选自与VFC-1、VFC-2、VFC-3、VFC-4、VFC- 5、VFC-6、VFC-7、VFC-8、VFC-9、VFC-10、VFC-11、V FC-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-4 7、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、VF C-71、VFC-72、VFC-73、VFC-74、VFC-75、VFC-76、VFC-77、VFC-78、VFC-79、VFC-80、VFC-81、VFC-82、V FC-83、VFC-84、VFC-85、VFC-86、VFC-87、VFC-88、 VFC-89或VFC-90中的任一者相关联的突变的一个或多个突变的一个或多个突变。,

[0101] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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 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, 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, VFC-87, VFC-88, VFC-89, VFC-90, or any 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 the 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 the 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 the 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 the 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the 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 the 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 the mutations 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 the 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 the 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the 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 the 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 the 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 the 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 the 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 the 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 the mutations 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 the mutations 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 the mutations 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 the 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 the 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the 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 the 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations 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 the mutations associated with VFC-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: 88, provided that 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 an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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-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 the mutations 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 the mutations 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 the mutations 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 the mutations associated with VFC-90.

[0102] 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 the amino acid sequence of the polypeptide comprising SEQ ID NO: 88 (with the proviso that the variant IgG Fc polypeptide comprises a mutation selected from a mutation at one or more positions selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330, and any combination thereof, as compared to SEQ ID NO: 88) include a variant IgG Fc polypeptide comprising: a mutation selected from a mutation at one or more positions selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330, and any combination thereof, as compared to SEQ ID NO: 88; and one or more mutations in the amino acid sequence that are not mutations at one or more positions selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330, and any combination thereof, as compared to SEQ ID NO: 14.

[0103] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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 one or more positions selected from 233, 234, 235, 237, 238, 239, 240, 268, 269, 270, 271, 329, 330, and any combination thereof, as 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 233, as 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 234, as 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 235, as 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 237, as 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 238, as 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 239 as 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 240 as 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 268 as 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 as 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 270 as 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 271 as 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 329 as 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 330 as compared to SEQ ID NO: 88.

[0104] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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 the positions selected from 238, 269, 270, or 330 as 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 set of mutations at positions 238, 269, 270, and 330 as 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 the positions selected from 237, 238, 269, 270, or 330 as 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 set of mutations at positions 237, 238, 269, 270, and 330 as 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 the positions selected from 237, 238, 239, 269, 270, or 330 as 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 set of mutations at positions 237, 238, 239, 269, 270, and 330 as 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 the positions selected from 237, 238, 240, 269, 270, or 330 as 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 set of mutations at positions 237, 238, 240, 269, 270, and 330 as 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 the positions selected from 235, 238, 269, 270, or 330 as 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 set of mutations at positions 235, 238, 269, 270, and 330 as 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 the positions selected from 233, 235, 238, 269, 270, or 330 as 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 set of mutations at positions 233, 235, 238, 269, 270, and 330 as 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 the positions selected from 235, 238, 269, 270, or 330, and an insertion between positions 233 and 234 as 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 set of mutations at positions 235, 238, 269, 270, and 330, and an insertion between positions 233 and 234 as 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 the positions selected from 234, 235, 268, 271, or 329 as 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 set of mutations at positions 234, 235, 268, 271, and 329 as 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 the positions selected from 234, 235, 239, 268, 271, or 329 as 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 set of mutations at positions 234, 235, 239, 268, 271, and 329 as 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 the positions selected from 234 or 235 as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 234 and 235 as 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 the positions selected from 237 or 237 as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions 237 and 238 as compared to SEQ ID NO: 88.

[0105] In some embodiments, the variant IgG Fc polypeptide comprises a mutation at one or more of the positions selected from 233, L234, L235, G237, P238, S239, V240, H268, E269, D270, P271, P329, A330, and any combination thereof compared to SEQ ID NO: 14. In some embodiments, 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 a mutation at position L234 compared to SEQ ID NO: 88. In some embodiments, 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 a mutation at position G237 compared to SEQ ID NO: 88. In some embodiments, 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 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.

[0106] In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the positions selected from P238, E269, D270, or A330 compared 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 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the positions selected from G237, P238, E269, D270, or A330 compared 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 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the 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 a 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 a mutation at any one or more of the 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 a 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 a mutation at any one or more of the positions selected from L235, P238, E269, D270, or A330 compared 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 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the 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 a 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 a mutation at any one or more of the positions selected from L235, P238, E269, D270, or A330, and an insertion between positions E233 and L234, as compared 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, and an insertion between positions 233 and L234, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the positions selected from L234, L235, H268, P271, or P329, as compared 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, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the positions selected from L234, L235, S239, H268, P271, or P329, as compared 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, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation at any one or more of the positions selected from L234 or L235, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions L234 and L235, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions G237 and P238, as compared to SEQ ID NO: 88.

[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: 88, provided that the variant IgG Fc polypeptide comprises a mutation at one or more positions selected from E233, L234, L235, G237, P238, S239, V240, H268, E269, D270, P271, P329, A330, and any combination thereof, as 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, as 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, as 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, as 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 G237, as 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 P238, as 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 S239 as 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 V240 as 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 as 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 E269 as 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 D270 as 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 P271 as 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 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.

[0108] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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 the positions selected from P238, E269, D270, or A330 as 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 set of mutations at positions P238, E269, D270, and A330 as 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 the positions selected from G237, P238, E269, D270, or A330 as 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 set of mutations at positions G237, P238, E269, D270, and A330 as 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 the positions selected from G237, P238, S239, E269, D270, or A330 as 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 set of mutations at positions G237, P238, S239, E269, D270, and A330 as 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 the positions selected from G237, P238, V240, E269, D270, or A330 as 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 set of mutations at positions G237, P238, V240, E269, D270, and A330 as 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 the positions selected from L235, P238, E269, D270, or A330 as 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 set of mutations at positions L235, P238, E269, D270, and A330 as 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 the positions selected from E233, L235, P238, E269, D270, or A330 as 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 set of mutations at positions E233, L235, P238, E269, D270, and A330 as 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 the positions selected from L235, P238, E269, D270, or A330 as compared to SEQ ID NO:88, and an insertion between positions E233 and L234. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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 set of mutations at positions L235, P238, E269, D270, and A330 as compared to SEQ ID NO:88, and an insertion between positions E233 and L234. In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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 the positions selected from L234, L235, H268, P271, or P329 as 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 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 the 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 a 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 the positions selected from L234 or L235 compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations at positions L234 and 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, provided that the variant IgG Fc polypeptide comprises a mutation at any one or more of the 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.

[0109] In some embodiments, the variant IgG Fc polypeptide comprises one or more of the 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, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of L234F, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of L235E, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of L235V, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of G237D, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of G237E, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P238D, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P238G, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P238E, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of S239G, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of S239D, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of V240A, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of H268D, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of E269D, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of D270E, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P271G, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P329A, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of A330R, as 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.

[0110] In some embodiments, the variant IgG Fc polypeptide comprises a mutation set selected from the group consisting of:

[0111] the mutation set of P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0112] the mutation set of G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0113] the mutation set of G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0114] the mutation set of G237D, P238G, V240A, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0115] the mutation set of L235V, P238E, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0116] the mutation set of L235V, P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88, and an insertion of the amino acid sequence GEV between positions 233 and 234;

[0117] the mutation set of P238S, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0118] the mutation set of L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0119] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0120] the mutation set of G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0121] the mutation set of P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G as compared to SEQ ID NO: 88;

[0122] the mutation set of L234F and L235E as compared to SEQ ID NO: 88;

[0123] the mutation set of G237E and P238E as compared to SEQ ID NO: 88; or

[0124] any combination thereof.

[0125] In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of G237D, P238G, V240A, E269D, D270E, and A330R compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of L235V, P238E, E269D, D270E, and A330R compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of L235V, P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88, and an insertion of the amino acid sequence GEV between positions 233 and 234; in some embodiments, the variant IgG Fc polypeptide comprises a mutation set of P238S, E269D, D270E, and A330R compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of L234F and L235E compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of G237E and P238E compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88.

[0126] In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises one or more of the 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, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of L234F, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of L235E, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of L235V, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of G237D, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of G237E, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of P238D, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of P238G, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of P238E, as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of S239G, as compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of S239D compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of V240A compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of H268D compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of E269D compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of D270E compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of P271G compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of P329A compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation of A330R compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a 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.

[0127] In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set selected from the group consisting of:

[0128] the mutation set of P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0129] the mutation set of G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0130] the mutation set of G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO:88;

[0131] the mutation set of G237D, P238G, V240A, E269D, D270E, and A330R compared to SEQ ID NO:88;

[0132] the mutation set of L235V, P238E, E269D, D270E, and A330R compared to SEQ ID NO:88;

[0133] the mutation set of L235V, P238D, E269D, D270E, and A330R compared to SEQ ID NO:88, and the insertion of the amino acid sequence GEV between positions 233 and 234;

[0134] the mutation set of P238S, E269D, D270E, and A330R compared to SEQ ID NO:88;

[0135] the mutation set of L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO:88;

[0136] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO:88;

[0137] the mutation set of G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 14; or

[0138] the mutation set of P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 14;

[0139] the mutation set of L234F and L235E compared to SEQ ID NO:88;

[0140] the mutation set of G237E and P238E compared to SEQ ID NO:88; or

[0141] any combination thereof.

[0142] In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of P238D, E269D, D270E, and A330R as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of G237D, P238G, E269D, D270E, and A330R as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of G237D, P238S, S239G, E269D, D270E, and A330R as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of G237D, P238G, V240A, E269D, D270E, and A330R as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of L235V, P238E, E269D, D270E, and A330R as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of L235V, P238D, E269D, D270E, and A330R as compared to SEQ ID NO: 88, and an insertion of the amino acid sequence GEV between positions 233 and 234; in some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of P238S, E269D, D270E, and A330R as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of L234F, L235E, P329A, H268D, and P271G as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of L234F, L235E, S239D, P329A, H268D, and P271G as compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of L234F and L235E compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of G237E and P238E compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88.

[0143] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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 of the 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, as compared to SEQ ID NO: 88.

[0144] 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 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 as compared to SEQ ID NO: 88) include a variant IgG Fc polypeptide comprising: a mutation 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 as compared to SEQ ID NO: 88; and one or more mutations that are not 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 as compared to SEQ ID NO: 88.

[0145] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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 of L234F as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of L234F as 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 of L235E as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of L235E as 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 of G237D as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of G237D as 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 of G237E as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of G237E as 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 of P238D as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P238D as 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 of P238G as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P238G as 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 of P238E as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P238E as 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 of S239G as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of S239G as 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 of S239D as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of S239D as 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 of V240A as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of V240A as 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 of H268D as compared to SEQ ID NO:88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of H268D as 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 of E269D as compared to SEQ ID NO:88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of E269D as 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 of D270E as compared to SEQ ID NO:88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of D270E as 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 of P271G as compared to SEQ ID NO:88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P271G as 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 of P329A as compared to SEQ ID NO:88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P329A as 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 of A330R as compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of A330R as 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 as 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 as compared to SEQ ID NO: 88.

[0146] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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 group selected from:

[0147] the mutation group of P238D, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0148] the mutation group of G237D, P238G, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0149] the mutation group of G237D, P238S, S239G, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0150] the mutation group of G237D, P238G, V240A, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0151] the mutation group of L235V, P238E, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0152] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0153] the mutation set of P238D, E269D, D270E, A330R compared to SEQ ID NO: 88;

[0154] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0155] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0156] the mutation set of G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G compared to SEQ ID NO: 14;

[0157] the mutation set of P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 14;

[0158] the mutation set of L234F and L235E compared to SEQ ID NO: 88;

[0159] the mutation set of G237E and P238E compared to SEQ ID NO: 88; or

[0160] any combination thereof.

[0161] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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 mutation set P238D, E269D, D270E, and A330R as 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 mutation set G237D, P238G, E269D, D270E, and A330R as 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 mutation set G237D, P238S, S239G, E269D, D270E, and A330R as 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 mutation set G237D, P238G, V240A, E269D, D270E, and A330R as 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 mutation set L235V, P238E, E269D, D270E, and A330R as 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 mutation set of L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234 as 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 mutation set of P238S, E269D, D270E, and A330R as 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 mutation set of 234F, L235E, P329A, H268D, and P271G as 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 mutation set of L234F, L235E, S239D, P329A, H268D, and P271G as 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 mutation set of L234F and L235E as 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 mutation set of G237E and P238E as 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 mutation set of G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G as 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 mutation set of P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G as compared to SEQ ID NO: 88.

[0162] In some embodiments, the variant IgG Fc polypeptide comprises one or more of the 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 as compared to SEQ ID NO: 14, 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 mutation set as compared to SEQ ID NO: 88.

[0163] Non-limiting examples include a variant IgG Fc polypeptide 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, as 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 other than the set of mutations, as compared to 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, as compared to SEQ ID NO: 88; and 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 that are / are not 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, as compared to SEQ ID NO: 88.

[0164] In some embodiments, the variant IgG Fc polypeptide comprises a mutation of L234F 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of L235E 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of L235V 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of G237D 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of G237E 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P238D 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 compared to SEQ ID NO: 88 in addition to the set of mutations.In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P238G 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P238E 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of S239G 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of S239D 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of V240A 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of H268D 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 compared to SEQ ID NO: 14 in addition to the set of mutations.In some embodiments, the variant IgG Fc polypeptide comprises a mutation of E269D 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of D270E 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of P329A 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 compared to SEQ ID NO: 88 in addition to the set of mutations. In some embodiments, the variant IgG Fc polypeptide comprises a mutation of 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 compared to SEQ ID NO: 88 in addition to the set of mutations. 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, 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 compared to SEQ ID NO: 88 in addition to the set of mutations.

[0165] In some embodiments, the variant IgG Fc polypeptide comprises a set of mutations selected from:

[0166] the set of mutations P238D, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0167] the set of mutations G237D, P238G, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0168] the set of mutations G237D, P238S, S239G, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0169] the set of mutations G237D, P238G, V240A, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0170] the set of mutations L235V, P238E, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0171] the set of mutations L235V, P238D, E269D, D270E, and A330R as compared to SEQ ID NO: 88, and an insertion of the amino acid sequence GEV between positions 233 and 234;

[0172] the set of mutations P238S, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0173] the set of mutations L234F, L235E, P329A, H268D, and P271G as compared to SEQ ID NO: 88;

[0174] the set of mutations L234F, L235E, S239D, P329A, H268D, and P271G as compared to SEQ ID NO: 88;

[0175] the set of mutations G237D, P238G, V240A, E269D, D270E, A330R, L234F, L235E, P329A, H268D, and P271G as compared to SEQ ID NO: 14;

[0176] the set of mutations P238D, E269D, D270E, A330R, L234F, L235E, S239D, P329A, H268D, and P271G as compared to SEQ ID NO: 14;

[0177] a mutation set of L234F and L235E compared to SEQ ID NO: 88;

[0178] a mutation set of G237E and P238E compared to SEQ ID NO: 88; or

[0179] any combination thereof, 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 mutation set compared to SEQ ID NO: 88.

[0180] In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of P238D, 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 compared to SEQ ID NO: 88 in addition to the mutation set. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of G237D, P238G, 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 compared to SEQ ID NO: 88 in addition to the mutation set. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of 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 compared to SEQ ID NO: 88 in addition to the mutation set. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of G237D, P238G, V240A, 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 compared to SEQ ID NO: 88 in addition to the mutation set. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of 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 compared to SEQ ID NO: 88 in addition to the mutation set.In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of L235V, P238D, E269D, D270E, and A330R, and an insertion of the amino acid sequence GEV between positions 233 and 234 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 mutation set compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of P238S, 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 mutation set compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of 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 mutation set compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of L234F, L235E, S239D, 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 mutation set compared to SEQ ID NO: 88. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of L234F and L235E 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 mutation set compared to SEQ ID NO: 88.In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of G237E and P238E 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 compared to SEQ ID NO: 88 in addition to the mutation set. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of G237D, P238G, V240A, E269D, D270E, A330R, 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 compared to SEQ ID NO: 88 in addition to the mutation set. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of P238D, E269D, D270E, A330R, L234F, L235E, S239D, 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 compared to SEQ ID NO: 88 in addition to the mutation set.

[0181] 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, the substitution comprises swapping the CH2 region for a CH2 region of another IgG isotype. In some embodiments, the variant Fc molecule comprises a CH2 domain sequence that is at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identical to SEQ ID NO: 96-101. In some embodiments, the variant Fc molecule comprises a CH2 domain sequence that is at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identical to SEQ ID NO: 96. In some embodiments, the variant Fc molecule comprises a CH2 domain sequence that is 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, the variant Fc molecule comprises a CH2 domain sequence that is 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, the variant Fc molecule comprises a CH2 domain sequence that is 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, the variant Fc molecule comprises a CH2 domain sequence that is 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 molecule comprises a CH2 domain sequence that is at least 50%, at least 85%, at least 90%, at least 94%, at least 95%, or at least 99% identical to SEQ ID NO: 101.

[0182] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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 set selected from the group consisting of:

[0183] the mutation set of P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0184] the mutation set of G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0185] the mutation set of G237D, P238S, S239G, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0186] the mutation set of G237D, P238G, V240A, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0187] the mutation set of L235V, P238E, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0188] the mutation set of L235V, P238D, E269D, D270E, and A330R as compared to SEQ ID NO: 88, and an insertion of the amino acid sequence GEV between positions 233 and 234;

[0189] the mutation set of P238S, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0190] the mutation set of L234F, L235E, P329A, H268D, and P271G as compared to SEQ ID NO: 88;

[0191] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G as compared to SEQ ID NO: 88;

[0192] the mutation set of L234F and L235E as compared to SEQ ID NO: 88;

[0193] the mutation set of G237E and P238E as compared to SEQ ID NO: 88; or

[0194] any combination thereof,

[0195] 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.

[0196] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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 mutation set of P238D, E269D, D270E, and A330R as 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 NO: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 mutation set of G237D, P238G, E269D, D270E, and A330R as 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 NO: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 mutation set of G237D, P238S, S239G, E269D, D270E, and A330R as 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 NO: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 mutation set of G237D, P238G, V240A, E269D, D270E, and A330R as 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 NO: 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 mutation set of L235V, P238E, E269D, D270E, and A330R as 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 NO: 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 mutation set of L235V, P238D, E269D, D270E, and A330R as compared to SEQ ID NO: 88, 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 NO: 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 mutation set of P238S, E269D, D270E, and A330R as 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 NO: 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 mutation set of L234F, L235E, P329A, H268D, and P271G as 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 NO: 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 mutation set of L234F, L235E, S239D, P329A, H268D, and P271G as 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 NO: 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 mutation set of L234F and L235E as 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 NO: 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 mutation set of G237E and P238E as 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 NO: 96-101.

[0197] In some embodiments, the variant IgG Fc polypeptide comprises a mutation set selected from the group consisting of:

[0198] the mutation set of P238D, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0199] the mutation set of G237D, P238G, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0200] the mutation set of G237D, P238S, S239G, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0201] the mutation set of G237D, P238G, V240A, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0202] the mutation set of L235V, P238E, E269D, D270E, and A330R as compared to SEQ ID NO: 88;

[0203] a mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0204] a mutation set of P238S, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0205] a mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0206] a mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0207] a mutation set of L234F and L235E compared to SEQ ID NO: 88;

[0208] a mutation set of G237E and P238E compared to SEQ ID NO: 88; or

[0209] any combination thereof, 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 mutation set 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.

[0210] In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of P238D, 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 compared to SEQ ID NO: 88 in addition to the mutation set, 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of G237D, P238G, 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 compared to SEQ ID NO: 88 in addition to the mutation set, 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of 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 compared to SEQ ID NO: 88 in addition to the mutation set, 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 NO: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of G237D, P238G, V240A, 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 compared to SEQ ID NO: 88 in addition to the mutation set, 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of 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 compared to SEQ ID NO: 88 in addition to the mutation set, 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of L235V, P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88, and an insertion of the amino acid sequence GEV between positions 233 and 234, 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 compared to SEQ ID NO: 88 in addition to the mutation set, 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 NO: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of P238S, 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 compared to SEQ ID NO: 88 in addition to the mutation set, 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of 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 compared to SEQ ID NO: 88 in addition to the mutation set, 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises the mutation set of L234F, L235E, S239D, 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 compared to SEQ ID NO: 88 in addition to the mutation set, 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 NO: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of L234F and L235E 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 compared to SEQ ID NO: 88 in addition to the mutation set, 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises a mutation set of G237E and P238E 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 compared to SEQ ID NO: 88 in addition to the mutation set, 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 NO: 96-101.

[0211] In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set selected from the group consisting of:

[0212] a mutation set of P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0213] a mutation set of G237D, P238G, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0214] a mutation set of G237D, P238S, S239G, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0215] a mutation set of G237D, P238G, V240A, E269D, D270E, and A330R compared to SEQ ID NO: 88;

[0216] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0217] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0218] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0219] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0220] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0221] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88;

[0222] the mutation set of L234F, L235E, S239D, P329A, H268D, and P271G compared to SEQ ID NO: 88; or

[0223] any combination thereof,

[0224] 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.

[0225] In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the mutation set of P238D, E269D, D270E, and A330R 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the mutation set of G237D, P238G, E269D, D270E, and A330R 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the mutation set of G237D, P238S, S239G, E269D, D270E, and A330R 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the mutation set of G237D, P238G, V240A, E269D, D270E, and A330R 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 NO: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the mutation set of L235V, P238E, E269D, D270E, and A330R 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the mutation set of L235V, P238D, E269D, D270E, and A330R compared to SEQ ID NO: 88, 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the mutation set of P238S, E269D, D270E, and A330R 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises the mutation set of L234F, L235E, P329A, H268D, and P271G 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 NO: 96-101.In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of L234F, L235E, S239D, P329A, H268D, and P271G as 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of L234F and L235E as 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 NO: 96-101. In some embodiments, the variant IgG Fc polypeptide comprises a variant sequence of SEQ ID NO: 88, wherein the variant IgG Fc polypeptide comprises a mutation set of G237E and P238E as 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 NO: 96-101.

[0226] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is 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 of those provided in Table 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 an amino acid sequence 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 IDa polypeptide having an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the amino acid sequence of 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.

[0227] In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to wild-type IgG. In some embodiments, the binding affinity compared to wild-type IgG is reduced by at least 10%, 20%, 30%, 40%, 50%,A variant IgG Fc polypeptide having at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% amino acid sequence identity to the amino acid sequence of 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 has increased binding affinity to FcyRIIb but not FcyRIIa. In some embodiments, the variant IgG Fc polypeptide has at least 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% amino acid sequence identity to the amino acid sequence 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 compared to the binding affinity of a wild-type IgG.A variant IgG Fc polypeptide having the amino acid sequence of 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 has increased binding affinity to FcyRIIb but not FcyRIIa.

[0228] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence that is at least 80, 85, 86, 87, 88, 89, 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.

[0229] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid sequence selected from any of those provided in Table 4. In some embodiments, the variant IgG Fc polypeptide comprises 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: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135,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 IDthe 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 IgGThe 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 IDthe 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.

[0230] In some embodiments, the variant IgG Fc polypeptides provided herein in Table 4 have mutations that enhance or confer selective binding to FcyRIIb, but not FcyRIIa. In some embodiments, the mutations that enhance or confer selective binding to FcyRIIb, but not FcyRIIa, are any of those associated with VFC-1 through VFC-90.

[0231] Dimeric variant Fc molecules

[0232] In some embodiments, two (or more) linkers are covalently or noncovalently associated, e.g., to form a heterodimeric or homodimeric therapeutic compound. In some embodiments, a linker can comprise an Fc region and two Fc regions associated with one another. In some embodiments of a therapeutic compound comprising two linker regions, the linker regions can self-associate, e.g., as two identical Fc regions. In some embodiments of a therapeutic compound comprising two linker regions, the linker regions cannot or do not substantially self-associate, e.g., the two Fc regions can be members of a knob and hole pair. In some embodiments, a 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 those provided herein. In some embodiments, the hole mutation is such as those provided herein. In some embodiments, the knob mutation is such as those 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 those provided in any one of SEQ ID NOs: 76, 77, 81, or 83.

[0233] In some embodiments, a polypeptide can be associated with another polypeptide. In some embodiments, a polypeptide associated with another polypeptide forms a dimeric molecule.

[0234] In some embodiments, a dimer is a homodimeric molecule. In some embodiments, a dimer is a heterodimeric molecule.

[0235] As used herein, the term “noncovalently conjugated” can refer to a polypeptide tethered to another polypeptide by 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 provided herein.

[0236] As discussed herein, different domains, molecules, or polypeptides can be linked together with a linker domain or region. Any of the linker regions described herein can be used as a linker. A linker can be, e.g., a glycine / serine linker. In some embodiments, a linker can comprise one or more repeats of GGGGS (SEQ ID NO: 105). In some embodiments, a linker comprises 1, 2, 3, 4, or 5 repeats. In some embodiments, a linker comprises GGGGSGGGGS (SEQ ID NO: 106). In some embodiments, a linker comprises GGGGSGGGGSGGGGS (SEQ ID NO: 107). In some embodiments, a linker comprises: 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.

[0237] These peptide linkers are non-limiting examples, and other peptide linkers can also be used.

[0238] In some embodiments, the polypeptide forms a dimer. In some embodiments, the dimer is a homodimer. In some embodiments, the dimer is a heterodimer.

[0239] Non-limiting exemplary configurations of the therapeutic compound include the following (e.g., in order from N-terminus to C-terminus):

[0240] R1-Linker Region A-R2

[0241] R3-Linker Region B-R4,

[0242] wherein,

[0243] R1, R2, R3, and R4 each independently comprises an effector binding / modulating moiety, e.g., an anti-PD1 antibody, an anti-LAG3 antibody, an anti-CTLA4 antibody, an anti-FcyRIIb antibody; or is absent;

[0244] Linker region A and linker region B comprise moieties that can associate with one another, e.g., linker A and linker region B each comprise an Fc polypeptide, provided that there is an effector binding / modulating moiety and a specific targeting moiety. In addition, linker A and linker region B each comprise an Fc polypeptide selective for FcyRIIb. In some embodiments, the Fc polypeptide selective for FcyRIIb has increased selectivity for FcyRIIb. In some embodiments, the Fc polypeptide selective for FcyRIIb has increased affinity for FcyRIIb. In some embodiments, the Fc polypeptide selective for FcyRIIb has increased selectivity and affinity for FcyRIIb. In some embodiments, the Fc polypeptide selective for FcyRIIb has increased selectivity for FcyRIIb over FcyRIIa. In some embodiments, the Fc polypeptide selective for FcyRIIb has increased affinity for FcyRIIb over FcyRIIa. In some embodiments, the Fc polypeptide selective for FcyRIIb has increased selectivity and affinity for FcyRIIb over FcyRIIa. In some embodiments, neither linker region A nor linker region B is present.

[0245] In some embodiments, the dimer comprises the following structural formula:

[0246] R1-Linker Region A-R2

[0247] R3-Linker Region B-R4,

[0248] wherein,

[0249] R1, R2, R3, and R4 each independently comprise an effector binding / modulating moiety, e.g., an anti-PD1 antibody, an anti-LAG3 antibody, an anti-CTLA4 antibody, an anti-FcyRIIb antibody; or is absent; and

[0250] Linker region A and linker region B each indepen...

Claims

1. A variant IgG Fc polypeptide having at least 95% sequence identity to SEQ ID NO: 88, provided that the variant IgG Fc polypeptide comprises a mutation or a group 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 (according to EU numbering).

2. The variant IgG Fc polypeptide of claim 1, wherein the variant IgG Fc polypeptide comprises a mutation that enhances selective binding to FcγRIIβ but not FcγRIIα.

3. The variant IgG Fc polypeptide of claim 1 , wherein the variant IgG Fc polypeptide comprises a mutation group selected from the group consisting of: mutations at positions 237 and 238 compared to SEQ ID NO:88; mutations at positions 237, 238, 240, 269, 270, and 330 compared 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 compared 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 compared to SEQ ID NO:88; or Mutations at positions 234 and 235 compared to SEQ ID NO:88; or any combination thereof.

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 the group consisting of 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, as compared to SEQ ID NO:

88.

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

6. The variant IgG Fc polypeptide of any one of claims 1 to 5, 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.

7. The variant IgG Fc polypeptide according to claim 1, wherein the variant IgG Fc polypeptide comprises 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: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 IDThe amino acid sequence of 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 according to claim 1, wherein the variant IgG Fc polypeptide comprises an amino acid sequence that is identical to 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 IDNO: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, provided that the variant IgG Fc polypeptide comprises a mutation or a group 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 as compared to SEQ ID NO:

88.

9. The variant IgG Fc polypeptide according to claim 1, wherein the variant IgG Fc polypeptide comprises an amino acid sequence that is identical to 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 IDNO: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, provided that the variant IgG has at least 95% sequence identity compared to SEQ ID NO:

88. 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.

10. 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 can be a heterodimer or a homodimer.

11. 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 can be a heterodimer or a homodimer.

12. The variant IgG Fc polypeptide according to claim 10, wherein the first polypeptide of the dimer comprises 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:******, SEQ ID NO:74, SEQ ID NO:75, SEQ It seems there is an incomplete "SEQ" at the end of the original text. Please check and provide the complete content if needed for a more accurate translation.: an amino acid sequence of 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 The second polypeptide of the dimer comprises 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 IDNO: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 first polypeptide of the dimer and the second polypeptide of the dimer can be the same or different.

13. The variant IgG Fc polypeptide of claim 10, wherein the dimer comprises a first polypeptide and a second polypeptide, wherein: 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; 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; 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 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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 The first polypeptide comprises the amino acid sequence of SEQ ID NO: 87, and the second polypeptide comprises the amino acid sequence of SEQ ID NO:

87.

14. A polypeptide comprising an Fc variant according to 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. 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 glutamic acid (E) residue at position 237 and a glutamic acid (E) residue at position 238, wherein the positions are numbered according to EU.

16. 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 numbered according to EU.

17. 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 numbered according to EU.

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

40.

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

40.

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

102.

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

102.

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

77.

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

77.

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

103.

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

103.

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

86.

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

86.

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

104.

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

104.

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, wherein the first polypeptide and the second polypeptide are identical.

31. 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, wherein the first polypeptide and the second polypeptide are different.

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

33. The polypeptide of claim 32, wherein the inhibitory receptor effector domain is an antibody that binds to PD-1, LAG-3, or CTLA4. The polypeptide according to 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, provided that the variant IgG Fc polypeptide comprises a mutation or a group 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 as compared to SEQ ID NO:88; an inhibitory receptor effector domain; and FcγRII binds to the effector domain.

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

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

45. The method of claim 44, wherein the autoimmune disorder is selected from the group consisting of 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, type 1 diabetes, idiopathic inflammatory myopathy, giant cell arteritis, myocarditis, post-myocardial infarction syndrome, postpericardiotomy syndrome, subacute bacterial endocarditis, Membranous glomerulonephritis, antiglomerular 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, overlap connective tissue disease syndrome, polymyalgia rheumatica, autoimmune urticaria, bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, epidermolysis bullosa acquisita, nodular Erythema, antineutrophil cytoplasmic antibody-associated vasculitis, Henoch-Schonlein purpura, Cogan syndrome, Buerger disease, Susan disease, immune complex vasculitis, primary CNS vasculitis, pemphigoid gestationis, hidradenitis suppurativa, lichen planus, lichen sclerosus, linear IgA disease (LAD), morphea, pemphigus vulgaris, acute pityriasis lichenoides vulgaris, Mucha-Habermann disease, psoriasis, systemic scleroderma, vitiligo, Addison's disease, autoimmune polyglandular syndrome (APS) type 1, autoimmune polyglandular syndrome (APS) type 2, juvenile idiopathic arthritis, juvenile dermatomyositis, autoimmune brain disease, autoimmune polyglandular syndrome (APS) type 3, autoimmune pancreatitis (AIP), autoimmune thyroiditis, Ord's thyroiditis, Graves' disease, autoimmune oophoritis, endometriosis, autoimmune orchitis, Syndrome, autoimmune bowel disease, celiac disease, microscopic colitis, thrombocytopenia, obesity, pain, adult-onset Still's disease, ankylosing spondylitis, CREST syndrome, enthesitis-related arthritis, eosinophilic fasciitis, Felty syndrome, IgG4-related disease, juvenile arthritis, Lyme disease (chronic), mixed connective tissue disease (MCTD), relapsing rheumatic disease, 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 (IRAEs), sarcoidosis, neurological Sarcoidosis, 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 thrombotic thrombocytopenia, thrombotic thrombocytopenia, pernicious anemia, aplastic anemia, Evan's syndrome, autoimmune neutropenia, acquired von Hippel-Lindau syndrome Willibrand syndrome, recurrent morbid pregnancy, Rh mismatch, Barlow's concentric sclerosis, Bickerstaff encephalitis, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, Hashimoto encephalopathy, idiopathic inflammatory demyelinating disease, Lambert-Eaton myasthenic syndrome, primary biliary sclerosis, glomerulonephritis, glomerular basement membrane disease, multiple sclerosis, Oshtoran syndrome, pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS), progressive inflammatory neuropathy, restless legs syndrome, pemphigus foliaceus (including associated malodor), transplantation, antibody-mediated rejection, allograft Antibody hypersensitization, xenoantibody-mediated rejection, solid organ rejection, acute and chronic graft-versus-host disease, stiff-person syndrome, Sydenham chorea, transverse myelitis, autoimmune retinopathy, autoimmune uveitis, uveitis, Cogan syndrome, Graves' ophthalmopathy, amyotrophic lateral sclerosis (ALS), Parkinson's disease, autoimmune encephalitis, CNS vasculitis, chronic idiopathic demyelinating polyneuropathy (CIDP), keratitis, moderate uveitis, woody conjunctivitis, Mooren's ulcer, neuromyelitis optica, opsoclonus-myoclonus syndrome, optic neuritis, scleritis, Susac syndrome, sympathetic ophthalmia, Tolosa-Hunt syndrome, rheumatic heart disease,Chronic sinusitis with nasal polyps, allergic bronchopulmonary mycosis, hypersensitivity pneumonitis, rheumatoid arthritis-associated interstitial lung disease (RA-ILD), nonspecific interstitial pneumonia, allergic asthma, infectious diseases / vaccination, antibody-dependent enhancement (e.g., dengue virus infection), chronic meningitis, anti-myelin oligodendrocyte glycoprotein (MOG) disease, activated DLBCL, anti-drug antibodies, anti-gene therapy vector antibodies (anti-AAV antibodies), therapeutic biologic antibodies (cytokine antibodies), Antibodies, monoclonal antibodies, enzymes, coagulation factors), autoimmune inner ear diseases (AIED), Meniere's disease, Behçet'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 immune insufficiency, pyoderma gangrenosum, agammaglobulinemia, amyloidosis, amyotrophic lateral sclerosis, anti-tubular basement membrane nephritis, atopic allergy, atopic dermatitis, autoimmune peripheral neuropathy, Blau syndrome, Castleman disease, Chagas disease, chronic obstructive pulmonary disease, chronic relapsing multifocal osteomyelitis, complement component 2 deficiency, contact dermatitis, Cushing 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, woody conjunctivitis, Majeed syndrome, narcolepsy, Rasmussen encephalitis, schizophrenia, serum sickness, spondyloarthropathy, Sweet syndrome, Takayasu's arteritis, or any combination thereof.

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

47. The method of claim 46, wherein the cancer is a solid tumor or a liquid tumor, including but not limited to hematopoietic cancer, lymphoma, 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 of using a polypeptide to modulate a cellular interaction between a first cell and a second cell in a subject, the method comprising administering to the subject comprising the cells the polypeptide of any one of claims 1, 2, 3, 5, 7 to 13, 15 to 29, or 36 to 42, or a pharmaceutical composition comprising the same.

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

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

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