Polypeptides comprising protease-resistant FC domain, compositions and uses thereof

Abstract

Embodiments provided herein, provide for methods and pharmaceutical compositions comprising polypeptides and molecules comprising a polypeptide having protease activity and a variant Fc molecule, and additional therapeutic, and methods that can be used to treat disorders, such as IgG mediated disorders.

Description

[0001] POLYPEPTIDES COMPRISING PROTEASE-RESISTANT FC DOMAIN, COMPOSITIONS AND USES THEREOF

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to U.S. Provisional Application No. 63 / 650,654, filed May 22, 2024, and U.S. Provisional Application No. 63 / 715,938, filed November 4, 2024, each of which is hereby incorporated by reference in its entirety

[0004] REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0005] The instant application contains a Sequence Listing which has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. Said XML copy, created on May 21, 2024, is named “SES-015USPR_SEQ.xml” and is 1,694,134 bytes in size.

[0006] FIELD

[0007] The embodiments provided herein relate to methods and compositions for treating a disease or a disorder in a subject in need thereof, comprising administering to the subject an IgG protease, and an enzyme replacement therapy (ERT) or a therapeutic antibody comprising a protease-resistant Fc domain.

[0008] BACKGROUND

[0009] Simultaneous administration of an IgG protease with approved biologies (e.g., TNF inhibitors like Humira and Enbrel, cytokine inhibitors such as Skyrizi, or B-cell depleters including Rituximab) is currently infeasible because the IgG protease cleaves the Fc domain of said biologies, accelerating their clearance and diminishing their therapeutic efficacy. However, this limitation may be overcome by introducing specific modifications to confer resistance against cleavage by the IgG protease. Accordingly, these biologic variants maintain their therapeutic integrity when administered concurrently with the IgG protease. Consequently, the engineered biologies with protease-resistant Fc domains facilitate combination therapy, potentially enhancing treatment efficacy for autoimmune conditions. The embodiments provided for herein fulfill this need as well as others. SUMMARY

[0010] Provided herein is a method of treating a disease or a disorder in a subject in need thereof, the method comprising administering to the subject: (a) an IgG protease; and (b) an enzyme replacement therapy (ERT), or a therapeutic antibody, wherein: the ERT is a recombinant enzyme linked to an Fc domain comprising a mutation, or a set of mutations of Y296Q, F296Q, and / or P329K according to EU numbering, and the therapeutic antibody comprises an IgG heavy chain Fc domain comprising a mutation, or a set of mutations of Y296Q, F296Q, and / or P329K in the Fc domain of the heavy chain, according to EU numbering.

[0011] In some embodiments, provided herein is a method of treating a disease or a disorder in a subject in need thereof, the method comprising administering to the subject: (a) an IgG protease comprising an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 55-1019; and (b) an enzyme replacement therapy (ERT), or a therapeutic antibody, wherein: the ERT is a recombinant enzyme linked to an Fc domain comprising a mutation, or a set of mutations of Y296Q, F296Q, and / or P329K according to EU numbering, and the therapeutic antibody comprises an IgG heavy chain Fc domain comprising a mutation, or a set of mutations of Y296Q, F296Q, and / or P329K in the Fc domain of the heavy chain, according to EU numbering.

[0012] In some embodiments, provided herein is a method of reducing immunoglobulins in a subject in need thereof; treating a transplant subject in need thereof; improving a gene-therapy in subject in need thereof; treating a subject having, or at risk, or elevated risk, for having, an IgG mediated disease or disorder; or cleaving B cell receptor in a subject in need thereof, the method comprising administering to the subject: (a) an IgG protease and comprising an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 55-1019; and (b) an enzyme replacement therapy (ERT), or a therapeutic antibody, wherein: the ERT is a recombinant enzyme linked to an Fc domain comprising a mutation, or a set of mutations of Y296Q, F296Q, and / or P329K according to EU numbering, and the therapeutic antibody comprises an TgG heavy chain Fc domain comprising a mutation, or a set of mutations of Y296Q, F296Q, and / or P329K in the Fc domain of the heavy chain, according to EU numbering.

[0013] DETAILED DESCRIPTION

[0014] This application incorporates by reference U.S. Non-Provisional Application No. 18 / 512,556, filed November 17, 2023, now U.S. Patent No. 12,091,694, issued September 17, 2024, U.S. Non-Provisional Application No. 18 / 815,585, filed August 26, 2024, U.S. NonProvisional Application No. 18 / 405,861, filed January 5, 2024, now U.S. Patent No. 12,129,499, issued October 29, 2024, U.S. Non-Provisional Application No. 18 / 885,268, filed September 13, 2024, International Application Nos. PCT / US2023 / 080313, filed November 17, 2023, and PCT / US2024 / 010503, filed January 5, 2024, each of which is hereby incorporated by reference in its entirety.

[0015] As used herein and in the appended claims, the singular forms “a”, “an” and “the” include plural reference unless the context clearly dictates otherwise.

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

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

[0018] As used herein, the term “contacting” means bringing together of two elements in an in vitro system or an in vivo system. For example, “contacting” a therapeutic compound with an individual or patient or cell includes the administration of the compound to an individual or patient, such as a human, as well as, for example, introducing a compound into a sample containing a cellular or purified preparation containing target.

[0019] As used herein, the terms “comprising” (and any form of comprising, such as “comprise”, “comprises”, and “comprised”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”), or “containing” (and any form of containing, such as “contains” and “contain”), arc inclusive or open-ended and do not exclude additional, unrecited elements or method steps. Any composition or method that recites the term “comprising” should also be understood to also describe such compositions as consisting, consisting of, or consisting essentially of the recited components or elements.

[0020] “Enzyme replacement therapy” or “ERT” refers to the use of a pharmaceutical composition that is administered to a subject that comprises one or more enzymes to the subject. In some embodiments, the enzyme is being administered to supplement or replace an enzyme that is missing or deficient in some aspect in the subject. Typically, the enzyme or enzymes involved in the therapy are administered to a subject by intravenous infusion of a pharmaceutical composition comprising the enzyme or enzymes. As described herein, the enzyme replacement therapy can be administered along with a pharmaceutical composition or a polypeptide, such as those provided herein. In some embodiments, the administration of the enzyme replacement therapy can be before, during, or after the administration of the pharmaceutical composition or the polypeptide, such as those provided herein.

[0021] As used herein, the term “fused” or “linked” when used in reference to a protein or molecule having different domains or heterologous sequences means that the protein domains are part of the same peptide chain that are connected to one another with either peptide bonds or other covalent bonding. The domains or section can be linked or fused directly to one another or another domain or peptide sequence can be between the two domains or sequences and such sequences would still be considered to be fused or linked to one another.

[0022] As used herein, the term “individual,” “subject,” or “patient,” used interchangeably, means any animal, including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, such as humans.

[0023] As used herein, the term “inhibit” refers to a result, symptom, or activity being reduced as compared to the activity or result in the absence of the compound that is inhibiting the result, symptom, or activity. In some embodiments, the result, symptom, or activity, is inhibited by about, or, at least, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99%. An result, symptom, or activity can also be inhibited if it is completely elimination or extinguished. As used herein, the phrase “in need thereof’ means that the subject has been identified as having a need for the particular method or treatment. In some embodiments, the identification can be by any means of diagnosis. In any of the methods and treatments described herein, the subject can be in need thereof. In some embodiments, the subject is in an environment or will be traveling to an environment in which a particular disease, disorder, or condition is prevalent.

[0024] As used herein, the phrase “integer from X to Y” means any integer that includes the endpoints. For example, the phrase “integer from 1 to 5” means 1, 2, 3, 4, or 5.

[0025] As used herein, the phrase “ophthalmically acceptable” means having no persistent detrimental effect on the treated eye or the functioning thereof, or on the general health of the subject being treated. However, it will be recognized that transient effects such as minor irritation or a “stinging” sensation are common with topical ophthalmic administration of drugs and the existence of such transient effects is not inconsistent with the composition, formulation, or ingredient (e.g., excipient) in question being “ophthalmically acceptable” as herein defined. In some embodiments, the pharmaceutical compositions can be ophthalmically acceptable or suitable for ophthalmic administration.

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

[0027] As used herein, the term “position,” is meant to refer to a location in the sequence of a polypeptide. Positions may be numbered sequentially, or according to an established format, for example the EU numbering system based on Kabat's amino acid positions. For example, position 298 is a position in the human antibody IgGl.

[0028] "Specific binding" or "specifically binds to" or is "specific for" a particular antigen, target, or an epitope means binding that is measurably different from a non-specific interaction. Specific binding can be measured, for example, by determining binding of a molecule compared to binding of a control molecule, which generally is a molecule of similar structure that does not have binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target.

[0029] Specific binding for a particular antigen, target, or an epitope can be exhibited, for example, by an antibody having a KD for an antigen or epitope of at least about 104M, at least about 10’5M, at least about 10'6 M, at least about 10"7M, at least about 10‘8M, at least about 10’9M, alternatively at least about 10'10 M, at least about 10'11M, at least about 10‘12M, or greater, where KD refers to a dissociation rate of a particular antibody-target interaction. Typically, an antibody that specifically binds an antigen or target will have a KD that is, or 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.

[0030] In some embodiments, specific binding for a particular antigen, target, or an epitope can be exhibited, for example, by an antibody having a KA or Kafor a target, antigen, or epitope of 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 a control, where KA or Karefers to an association rate of a particular antibody-antigen interaction.

[0031] As provided herein, the compounds and compositions provided for herein can be used in methods of treatment as provided herein. As used herein, the terms “treat,” “treated,” or “treating” mean both therapeutic treatment and prophylactic measures wherein the object is to slow down (lessen) an undesired physiological condition, disorder or disease, or obtain beneficial or desired clinical results. For purposes of these embodiments, beneficial or desired clinical results include, but are not limited to, alleviation 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 or remission (whether partial or total), whether detectable or undetectable; an amelioration of at least one measurable physical parameter, not necessarily discernible by the patient; or enhancement or improvement of condition, disorder or disease. Treatment includes eliciting a clinically significant response without excessive levels of side effects. Treatment also includes prolonging survival, as applicable for a specific disease, as compared to expected survival if not receiving treatment. Thus, “treatment of an autoimmune condition” or “treating autoimmunity” means an activity that alleviates or ameliorates any of the primary phenomena or secondary symptoms associated with the autoimmune condition other condition described herein when the terms “treat,” “treated,” or “treating” are used in conjunction with such condition. As used herein, terms “variant,” “molecule,” “therapeutic,” “therapeutic compound,” “compound,” “polypeptide,” or “protein” can be used interchangeably and relate to the variants, molecules, therapeutics, therapeutic compounds, compounds, polypeptides, and proteins disclosed herein.

[0032] Therapeutic Antibodies

[0033] Simultaneous administration of IgG proteases, such as IdeS or its variants, with approved therapeutic biologies, such as, but not limited to, those provided for herein, is currently infeasible due to proteolytic cleavage of the Fc domains of said therapeutic biologies by the IgG protease. Specifically, the IgG protease cleaves conserved regions within the Fc domain of these therapeutic biologies, resulting in accelerated clearance from circulation and significantly diminished therapeutic efficacy. As a result, effective combination therapy involving these biologies and IgG proteases remains challenging in practice. To address this limitation, targeted modifications may be introduced into the Fc domain of these biologies, conferring resistance against cleavage by IgG proteases. These engineered biologic variants, characterized by strategically altered amino acid sequences, retain their structural therapeutic functionality even when co-administered with IgG proteases. Thus, protease-resistant biologies facilitate concurrent administration regimens, enabling synergistic therapeutic strategies previously unattainable due to the proteolytic instability of conventional Fc domains. Consequently, the development of such engineered biologies with protease-resistant Fc domains enhances the feasibility and efficacy of combination therapy approaches. This advancement has significant implications for treatment of diseases or disorders, such as, but not limited to, autoimmune and inflammatory conditions.

[0034] Accordingly, the polypeptides, such as IgG protease, provided herein may be coadministered with other therapeutics. In some embodiments, the IgG protease provided for herein may be chronically administered with other therapeutics, such as enzyme replacement therapeutics or therapeutic antibodies, such as those provided for herein. In some embodiments, the other therapeutic is a therapeutic antibody. In some embodiments, the therapeutic antibody is an antibody used for treatment of a disease, such as and without limitation, cancer, autoimmune diseases, infectious diseases, inflammatory diseases, cardiovascular diseases, neurological disorders, ophthalmic diseases, and respiratory diseases. In some embodiments, the therapeutic antibody is selected from Table 1.

[0035] The therapeutic antibodies provided for herein arc known in the art. Thus, in some embodiments, all elements of the therapeutic antibody, such as and without limitation, heavy chains, light chains, variable regions, constant regions, antigen-binding sites, the Fc region, the hinge region, disulfide bonds, glycosylation sites, and framework regions may be known in the art. In some embodiments, the heavy chain (HC) and light chain (LC) of each therapeutic antibody provided for herein, without limitation in Table 1, is known in the art. As used herein, the therapeutic antibody selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Dupixent (dupilumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Tysabri (natalizumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Taltz (ixekizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Prolia (denosumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Haris (canakinumab), Arcalyst (rilonacept), Omvoh (mirikizumab), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spevigo (spesolimab), Cinqair (reslizumab), Kevzara (sarilumab), Sylvant (siltuximab), Adbry (tralokinumab), Ebglyss (lebrikizumab), is meant to comprises a heavy chain (HC) and a light chain (LC) each of which is known in the art to be the heavy chain (HC) and the light chain (LC) of said therapeutic antibody. In some embodiments, the therapeutic antibody selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Dupixent (dupilumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Tysabri (natalizumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Taltz (ixckizumab), Bimzclx (bimckizumab), Nucala (mcpolizumab), Fascnra (bcnralizumab), Prolia (denosumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Haris (canakinumab), Arcalyst (rilonacept), Omvoh (mirikizumab), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spevigo (spesolimab), Cinqair

[0036] (reslizumab), Kevzara (sarilumab), Sylvant (siltuximab), Adbry (tralokinumab), Ebglyss (lebrikizumab), is meant to comprises a heavy chain (HC) comprising mutations to the Fc domain of the heavy chain, such as those provided for herein, and a light chain (LC) known in the art to be the light chain (LC) of said therapeutic antibody. Accordingly, in some embodiments, the therapeutic antibody selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Dupixent (dupilumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Tysabri (natalizumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Taltz (ixekizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (bcnralizumab), Prolia (denosumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab- CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Haris (canakinumab), Arcalyst (rilonacept), Omvoh (mirikizumab), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spevigo (spesolimab), Cinqair (reslizumab), Kevzara (sarilumab), Sylvant (siltuximab), Adbry (tralokinumab), Ebglyss (lebrikizumab), comprises a heavy chain (HC) comprising mutations, such as those provided for herein, to the Fc domain of the heavy chain that render the Fc domain resistant to proteolytic cleavage, and a light chain (LC) known in the art to be the light chain (LC) of said therapeutic antibody.

[0037] In some embodiments, the therapeutic antibody of Table 1 comprises a heavy chain (HC) amino acid sequence as shown in Table 1, column 4, or a variant thereof. In some embodiments, the therapeutic antibody of Table 1 comprises a heavy chain (HC) amino acid sequence In some embodiments, the heavy chain (HC) amino acid sequence comprises an Fc domain as shown in Table 1, column 4, or a variant thereof. In some embodiments, the therapeutic antibody comprising an Fc domain further comprises a mutation, or at least one mutation, that render the Fc domain resistant to proteolytic cleavage. In some embodiments, the therapeutic antibody comprising an Fc domain further comprises a mutation, or at least one mutation, that render the Fc domain resistant to proteolytic cleavage by a protease, such as those provided herein.

[0038] In some embodiments, a therapeutic antibody comprising an Fc domain comprises a mutation corresponding to Y296Q mutation, according to EU numbering. In some embodiments, a therapeutic antibody comprising an Fc domain comprises a mutation corresponding to F296Q mutation, according to EU numbering. In some embodiments, a therapeutic antibody comprising an Fc domain comprises a mutation corresponding to P329K mutation, according to EU numbering. In some embodiments, a therapeutic antibody comprising an Fc domain comprises a set of mutations corresponding to Y296Q and P329K mutations, according to EU numbering. In some embodiments, a therapeutic antibody comprising an Fc domain comprises a set of mutations corresponding to F296Q and P329K mutations, according to EU numbering.

[0039] In some embodiments, positions 296 and / or 329, according to EU numbering, may be represented as linear positions in the Fc domain amino acid sequence of the therapeutic antibody heavy chain sequence. For example, and without limitation, Rituxan (rituximab) comprises the Fc domain amino acid sequence shown in Table 1, and accordingly, position 296, according to EU numbering, corresponds to position 179 in the linear amino acid sequence of the Fc domain, and position 329, according to EU numbering, corresponds to position 212 in the linear amino acid sequence of the Fc domain, as shown in Table 1. Similar linear representation of each position 296 and / or 329, according to EU numbering, may be conducted for any Fc domain amino acid sequence as shown in Table 1, regardless of immunoglobulin isotype, by assigning position 1 to the first amino acid in the Fc domain sequence as shown in Table 1.

[0040] In some embodiments, the therapeutic antibody selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Haris (canakinumab), Arcalyst (rilonacept), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spevigo (spesolimab), Kevzara (sarilumab), Sylvant (siltuximab), any combination thereof, and any variant thereof, comprises a mutation corresponding to Y296Q mutation in the Fc domain, according to EU numbering.

[0041] In some embodiments, the therapeutic antibody selected from Dupixent (dupilumab), Tysabri (natalizumab), Taltz (ixekizumab), Prolia (denosumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Omvoh (mirikizumab), Cinqair (reslizumab), Adbry (tralokinumab), Ebglyss (lebrikizumab), and any variant thereof, comprises a mutation corresponding to F296Q mutation in the Fc domain, according to EU numbering.

[0042] In some embodiments, the therapeutic antibody selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Dupixent (dupilumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Tysabri (natalizumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Taltz (ixekizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Prolia (denosumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Haris (canakinumab), Arcalyst (rilonacept), Omvoh (mirikizumab), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spevigo (spesolimab), Cinqair (reslizumab), Kevzara (sarilumab), Sylvant (siltuximab), Adbry (tralokinumab), Ebglyss (lebrikizumab), and any variant thereof, comprises a mutation corresponding to P329K mutation in the Fc domain, according to EU numbering.

[0043] In some embodiments, the therapeutic antibody selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Haris (canakinumab), Arcalyst (rilonacept), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spevigo (spesolimab), Kevzara (sarilumab), Sylvant (siltuximab), and any variant thereof, comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain, according to EU numbering.

[0044] In some embodiments, the therapeutic antibody selected from Dupixent (dupilumab), Tysabri (natalizumab), Taltz (ixekizumab), Prolia (denosumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Omvoh (mirikizumab), Cinqair (reslizumab), Adbry (tralokinumab), and Ebglyss (lebrikizumab), and any variant thereof, comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain, according to EU numbering.

[0045] In some embodiments, the therapeutic antibody selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Haris (canakinumab), Arcalyst (rilonacept), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spevigo (spesolimab), Kevzara (sarilumab), Sylvant (siltuximab), and any variant thereof, comprises a heavy chain comprising a mutation corresponding to Y 296Q mutation in the Fc domain of the heavy chain, according to EU numbering.

[0046] In some embodiments, the therapeutic antibody Rituxan (rituximab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ocrevus (ocrelizumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Orencia (abatacept) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Stelara (ustekinumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Cosentyx (secukinumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Tremfya (guselkumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Skyrizi (risankizumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Actemra (tocilizumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Enbrel (etanercept) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Humira (adalimumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Benlysta (belimumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Saphnelo (anifrolumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Xolair (omalizumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Bimzelx (bimekizumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Nucala (mepolizumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Fasenra (benralizumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Remicade (infliximab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Simponi (golimumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. Tn some embodiments, the therapeutic antibody Entyvio (vedolizumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Briumvi (ublituximab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Orthoclone Okt3 (Muromonab-CD3) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody MabCampath / Lemtrada (lemtuzumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Alzumab (itolizumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Haris (canakinumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Arcalyst (rilonacept) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ilumya (tildrakizumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Simulect (basiliximab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Zenapax (daclizumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Spevigo (spesolimab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Kevzara (sarilumab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Sylvant (siltuximab) comprises a heavy chain comprising a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering.

[0047] In some embodiments, the therapeutic antibody selected from Dupixent (dupilumab), Tysabri (natalizumab), Taltz (ixekizumab), Prolia (denosumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Omvoh (mirikizumab), Cinqair (reslizumab), Adbry (tralokinumab), and Ebglyss (lebrikizumab), comprises a heavy chain comprising a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering.

[0048] In some embodiments, the therapeutic antibody Dupixent (dupilumab) comprises a heavy chain comprising a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Tysabri (natalizumab) comprises a heavy chain comprising a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Taltz (ixekizumab) comprises a heavy chain comprising a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Prolia (denosumab) comprises a heavy chain comprising a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Veopoz (pozelimab) comprises a heavy chain comprising a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Soliris (eculizumab) comprises a heavy chain comprising a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Siliq (brodalumab) comprises a heavy chain comprising a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Omvoh (mirikizumab) comprises a heavy chain comprising a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Cinqair (reslizumab) comprises a heavy chain comprising a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Adbry (tralokinumab) comprises a heavy chain comprising a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ebglyss (lebrikizumab) comprises a heavy chain comprising a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering.

[0049] In some embodiments, the therapeutic antibody selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Dupixent (dupilumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Tysabri (natalizumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Taltz (ixekizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Prolia (denosumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Haris (canakinumab), Arcalyst (rilonacept), Omvoh (mirikizumab), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spevigo (spesolimab), Cinqair (reslizumab), Kevzara (sarilumab), Sylvant (siltuximab), Adbry (tralokinumab), Ebglyss (lebrikizumab), and any variant thereof, comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Rituxan (rituximab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ocrevus (ocrelizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Orencia (abatacept) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Stelara (ustekinumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Cosentyx (secukinumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Tremfya (guselkumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Skyrizi (risankizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Actemra (tocilizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Enbrel (etanercept) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Humira (adalimumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Benlysta (belimumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Saphnelo (anifrolumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Xolair (omalizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Bimzelx (bimekizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Nucala (mepolizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Fasenra (benralizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Remicade (infliximab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Simponi (golimumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Enty vio (vedolizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. Tn some embodiments, the therapeutic antibody Briumvi (ublituximab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Orthoclone Okt3 (Muromonab-CD3) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody MabCampath / Lemtrada (lemtuzumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Alzumab (itolizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Haris (canakinumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Arcalyst (rilonacept) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ilumya (tildrakizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Simulect (basiliximab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Zenapax (daclizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Spevigo (spesolimab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Kevzara (sarilumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Sylvant (siltuximab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Dupixent (dupilumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Tysabri (natalizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Taltz (ixekizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Prolia (denosumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Veopoz (pozelimab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Soliris (eculizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Siliq (brodalumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Omvoh (mirikizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Cinqair (reslizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Adbry (tralokinumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ebglyss (lebrikizumab) comprises a heavy chain comprising a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering.

[0050] In some embodiments, the therapeutic antibody selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Haris (canakinumab), Arcalyst (rilonacept), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spcvigo (spcsolimab), Kcvzara (sarilumab), Sylvant (siltuximab), and any variant thereof, comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody selected from Dupixent (dupilumab), Tysabri (natalizumab), Taltz (ixekizumab), Prolia (denosumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Omvoh (mirikizumab), Cinqair (reslizumab), Adbry (tralokinumab), and Ebglyss (lebrikizumab), and any variant thereof, comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering.

[0051] In some embodiments, the therapeutic antibody Rituxan (rituximab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ocrevus (ocrelizumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Orencia (abatacept) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Stelara (ustekinumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Cosentyx (secukinumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Tremfya (guselkumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Skyrizi (risankizumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Actemra (tocilizumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Enbrel (etanercept) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Humira (adalimumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Benlysta (belimumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Saphnelo (anifrolumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Xolair (omalizumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Bimzelx (bimekizumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Nucala (mepolizumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Fasenra (benralizumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Remicade (infliximab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Simponi (golimumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Entyvio (vedolizumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Briumvi (ublituximab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Orthoclone Okt3 (Muromonab-CD3) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody MabCampath / Lemtrada (lemtuzumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Alzumab (itolizumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Haris (canakinumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Arcalyst (rilonacept) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ilumya (tildrakizumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Simulect (basiliximab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Zenapax (daclizumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Spevigo (spesolimab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Kevzara (sarilumab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Sylvant (siltuximab) comprises a heavy chain comprising a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Dupixent (dupilumab) comprises a heavy chain comprising a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Tysabri (natalizumab) comprises a heavy chain comprising a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Taltz (ixekizumab) comprises a heavy chain comprising a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Prolia (denosumab) comprises a heavy chain comprising a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Veopoz (pozelimab) comprises a heavy chain comprising a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Soliris (eculizumab) comprises a heavy chain comprising a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Siliq (brodalumab) comprises a heavy chain comprising a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Omvoh (mirikizumab) comprises a heavy chain comprising a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Cinqair (reslizumab) comprises a heavy chain comprising a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Adbry (tralokinumab) comprises a heavy chain comprising a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ebglyss (lebrikizumab) comprises a heavy chain comprising a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering.

[0052] In some embodiments, the therapeutic antibody selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Haris (canakinumab), Arcalyst (rilonacept), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spcvigo (spcsolimab), Kcvzara (sarilumab), Sylvant (siltuximab), and any variant thereof, comprises a heavy chain 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 to an amino acid sequence of Table 1, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Rituxan (rituximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1353, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ocrevus (ocrelizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1355, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Orencia (abatacept) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1359, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Stelara (ustekinumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1365, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Cosentyx (secukinumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1366, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Tremfya (guselkumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1372, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Skyrizi (risankizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1374, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Skyrizi (risankizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1375, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Skyrizi (risankizumab) comprises a set of heavy chains having amino acid sequences that are 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 to an amino acid sequences of SEQ ID NOs: 1374 and 1375, provided that each amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Actemra (tocilizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1384, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Enbrel (etanercept) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1389, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Humira (adalimumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1390, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Benlysta (belimumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1352, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Saphnelo (anifrolumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1362, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Saphnelo (anifrolumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1363, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbcring.In some embodiments, the therapeutic antibody Saphnclo (anifrolumab) comprises a set of heavy chains having amino acid sequences that are 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 to an amino acid sequences of SEQ ID NOs: 1362 and 1363, provided that each amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Xolair (omalizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1364, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Bimzelx (bimekizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1368, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Nucala (mepolizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1381, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Fasenra (benralizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1383, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Remicade (infliximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1388, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Simponi (golimumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1391, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Entyvio (vedolizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1392, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Briumvi (ublituximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1354, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Orthoclone Okt3 (Muromonab-CD3) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1356, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody MabCampath / Lemtrada (lemtuzumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1357, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Alzumab (itolizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1358, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Haris (canakinumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1370, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Arcalyst (rilonacept) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1371, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ilumya (tildrakizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1376, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Simulect (basiliximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1377, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Zcnapax (daclizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1378, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Spevigo (spesolimab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1379, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Kevzara (sarilumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1385, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Sylvant (siltuximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1386, provided that the amino acid sequence comprises a mutation corresponding to Y296Q mutation in the Fc domain of the heavy chain, according to EU numbering.

[0053] In some embodiments, the therapeutic antibody selected from Dupixent (dupilumab), Tysabri (natalizumab), Taltz (ixekizumab), Prolia (denosumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Omvoh (mirikizumab), Cinqair (reslizumab), Adbry (tralokinumab), and Ebglyss (lebrikizumab), and any variant thereof, comprises a heavy chain 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 to an amino acid sequence of Table 1 , provided that the amino acid sequence comprises a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Dupixent (dupilumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1380, provided that the amino acid sequence comprises a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Tysabri (natalizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1351, provided that the amino acid sequence comprises a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Taltz (ixekizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1367, provided that the amino acid sequence comprises a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Prolia (denosumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1387, provided that the amino acid sequence comprises a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Veopoz (pozelimab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1360, provided that the amino acid sequence comprises a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Soliris (cculizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1361, provided that the amino acid sequence comprises a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Siliq (brodalumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1369, provided that the amino acid sequence comprises a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Omvoh (mirikizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1373, provided that the amino acid sequence comprises a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Cinqair (reslizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1382, provided that the amino acid sequence comprises a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Adbry (tralokinumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1393, provided that the amino acid sequence comprises a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ebglyss (lebrikizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1394, provided that the amino acid sequence comprises a mutation corresponding to F296Q mutation in the Fc domain of the heavy chain, according to EU numbering.

[0054] In some embodiments, the therapeutic antibody selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Dupixent (dupilumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Tysabri (natalizumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Taltz (ixekizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Prolia (denosumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Haris (canakinumab), Arcalyst (rilonacept), Omvoh (mirikizumab), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spevigo (spesolimab), Cinqair (reslizumab), Kevzara (sarilumab), Sylvant (siltuximab), Adbry (tralokinumab), and Ebglyss (lebrikizumab), comprises a heavy chain 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 to an amino acid sequence of Table 1, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Rituxan (rituximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1353, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ocrevus (ocrelizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1355, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Orencia (abatacept) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1359, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Stelara (ustekinumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1365, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Cosentyx (secukinumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1366, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Tremfya (guselkumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1372, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Skyrizi (risankizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1374, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Skyrizi (risankizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1375, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Skyrizi (risankizumab) comprises a set of heavy chains having amino acid sequences that are 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 to an amino acid sequences of SEQ ID NOs: 1374 and 1375, provided that each amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Actemra (tocilizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1384, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Enbrel (etanercept) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1389, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Humira (adalimumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1390, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Benlysta (belimumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1352, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Saphnelo (anifrolumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1362, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Saphnelo (anifrolumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1363, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Saphnelo (anifrolumab) comprises a set of heavy chains having amino acid sequences that are 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 to an amino acid sequences of SEQ ID NOs: 1362 and 1363, provided that each amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Xolair (omalizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1364, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Bimzelx (bimekizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1368, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Nucala (mepolizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1381, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Fasenra (benralizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1383, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Remicade (infliximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1388, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Simponi (golimumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1391, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Entyvio (vedolizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1392, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Briumvi (ublituximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1354, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Orthoclone Okt3 (Muromonab-CD3) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1356, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody MabCampath / Lemtrada (lemtuzumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1357, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Alzumab (itolizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1358, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Harris (canakinumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1370, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Arcalyst (rilonacept) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1371, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ilumya (tildrakizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1376, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Simulect (basiliximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1377, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Zenapax (daclizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1378, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Spevigo (spesolimab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1379, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Kevzara (sarilumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1385, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Sylvant (siltuximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1386, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Dupixent (dupilumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1380, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Tysabri (natalizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1351, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Taltz (ixekizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1367, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Prolia (denosumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1387, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. Tn some embodiments, the therapeutic antibody Veopoz (pozelimab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1360, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Soliris (eculizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1361, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Siliq (brodalumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1369, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Omvoh (mirikizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1373, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Cinqair (reslizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1382, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Adbry (tralokinumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1393, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ebglyss (lebrikizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1394, provided that the amino acid sequence comprises a mutation corresponding to P329K mutation in the Fc domain of the heavy chain, according to EU numbering.

[0055] In some embodiments, the therapeutic antibody selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Haris (canakinumab), Arcalyst (rilonacept), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spevigo (spesolimab), Kevzara (sarilumab), Sylvant (siltuximab), comprises a heavy chain 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 to an amino acid sequence of Table 1, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody selected from Dupixent (dupilumab), Tysabri (natalizumab), Taltz (ixekizumab), Prolia (denosumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Omvoh (mirikizumab), Cinqair (reslizumab), Adbry (tralokinumab), and Ebglyss (lebrikizumab), comprises a heavy chain 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 to an amino acid sequence of Table 1, provided that the amino acid sequence comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Rituxan (rituximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1353, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ocrevus (ocrelizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1355, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Orencia (abatacept) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1359, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Stelara (ustekinumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1365, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Cosentyx (secukinumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1366, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. Tn some embodiments, the therapeutic antibody Tremfya (gusclkumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1372, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Skyrizi (risankizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1374, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering.In some embodiments, the therapeutic antibody Skyrizi (risankizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1375, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering.In some embodiments, the therapeutic antibody Skyrizi (risankizumab) comprises a set of heavy chains having amino acid sequences that are 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 to an amino acid sequences of SEQ ID NOs: 1374 and 1375, provided that each amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Actemra (tocilizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1384, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Enbrel (etanercept) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1389, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Humira (adalimumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1390, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Benlysta (belimumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1352, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Saphnelo (anifrolumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1362, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Saphnelo (anifrolumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1363, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Saphnelo (anifrolumab) comprises a set of heavy chains having amino acid sequences that are 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 to an amino acid sequences of SEQ ID NOs: 1362 and 1363, provided that each amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Xolair (omalizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1364, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Bimzelx (bimekizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1368, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Nucala (mepolizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1381, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Fasenra (benralizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1383, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Remicade (infliximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1388, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Simponi (golimumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1391, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Entyvio (vedolizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1392, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Briumvi (ublituximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1354, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Orthoclone Okt3 (Muromonab-CD3) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1356, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody MabCampath / Lemtrada (lemtuzumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1357, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Alzumab (itolizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1358, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Haris (canakinumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1370, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Arcalyst (rilonacept) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1371, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ilumya (tildrakizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1376, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Simulect (basiliximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1377, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Zenapax (daclizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1378, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Spevigo (spesolimab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1379, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Kevzara (sarilumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1385, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Sylvant (siltuximab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1386, provided that the amino acid sequence comprises a set of mutations corresponding to Y296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Dupixent (dupilumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1380, provided that the amino acid sequence comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Tysabri (natalizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1351, provided that the amino acid sequence comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Taltz (ixekizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1367, provided that the amino acid sequence comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Prolia (denosumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1387, provided that the amino acid sequence comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Veopoz (pozelimab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1360, provided that the amino acid sequence comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Soliris (eculizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1361, provided that the amino acid sequence comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Siliq (brodalumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1369, provided that the amino acid sequence comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Omvoh (mirikizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1373, provided that the amino acid sequence comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Cinqair (reslizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1382, provided that the amino acid sequence comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Adbry (tralokinumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1393, provided that the amino acid sequence comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the therapeutic antibody Ebglyss (lebrikizumab) comprises a heavy chain 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 to an amino acid sequence of SEQ ID NO: 1394, provided that the amino acid sequence comprises a set of mutations corresponding to F296Q and P329K mutations in the Fc domain of the heavy chain, according to EU numbering. In some embodiments, the Fc domain of the therapeutic antibody bears mutations to render the Fc domain “cffcctorlcss”. In some embodiments, mutations to render the Fc domain effectorless eliminate interaction with immune effector functions. Typically, the Fc region of an antibody mediates interactions with immune cell receptors (e.g., Fey receptors on macrophages, natural killer cells, neutrophils) and components of the complement system. These interactions trigger effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and release of pro-inflammatory mediators. Accordingly, in some embodiments, Fc domain that is effectorless is unable to bind FcRs. In some embodiments, Fc domain that has effector function is able to bind FcRs.

[0056] In some embodiments, the Fc domain does not bind to an Fey receptor. In some embodiments, the Fc domain does not bind to FcyRI, FcyRIIa, FcyRIIc, FcyRIIIa and / or FcyRIIb. In some embodiments, the Fc domain does not bind to FcyRI, FcyRIIa, FcyRIIc, and FcyRIIIa. In some embodiments, the Fc domain does not bind to FcyRIIb.

[0057] In some embodiments, the Fc domain does not significantly bind to an Fey receptor. In some embodiments, the Fc domain does not significantly bind to FcyRI, FcyRIIa, FcyRIIc, FcyRIIIa and / or FcyRIIb. In some embodiments, the Fc domain does not significantly bind to FcyRI, FcyRIIa, FcyRIIc, and FcyRIIIa. In some embodiments, the Fc domain does not significantly bind to FcyRIIb. The term "significantly," as used herein, refers to a reduction in receptor activation by an Fc with mutations to render the Fc domain effectorless when compared to an Fc domain with effector function. Specifically, "significantly" means that the effectorless Fc domain demonstrates a decrease in Fc receptor activation by at least or about 10%, 20%, 30%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% relative to an Fc domain with effector function.

[0058] In some embodiments, the Fc domain comprising a mutation, or set of mutations that confer protease-resistance, comprises a mutation, or set of mutations known to render the Fc domain effectorless. In some embodiments, the Fc domain comprising a mutation, or set of mutations that confer protease-resistance, such as those provided for herein, comprises a mutation, or set of mutations known to render the Fc domain effectorless, such as those known in the art. Accordingly, in some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises a mutation or set of mutations selected from the group consisting of: L234A, L23 A, L234F, L235E, P329G, P331S, N297A, N297G, N297Q, G236A, A330S, S239D, I332E, S267E, H268F, S324T, Y296W, T299A, V308P, H310A, R409K, Y435H, T307A, T309A, T309K, K322A, K326W, K334W, K326A, K334A, G237A, P238S, H268A, M252Y, S254T, T256E, M428L, N434A, E38OA, T250Q, or any combination thereof, according to EU numbering system. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises a mutation at L234 and / or L235 and / or G237. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises L234A and / or L235A mutations, which can be referred to as “LALA” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises L234A, L235A, and G237A mutations, which can be referred to as “LALA GA” or “AAA”. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises L234F, and L235E mutations, which can be referred to as “LAFE” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises L234A, L235A, and P329G mutations, which can be referred to as “LALAPG” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises L234A, L235A, P329G, and P331S mutations, which can be referred to as “LALAPGS” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises L234A, L235A, and P329S mutations, which can be referred to as “LALAPS” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises a N297A mutation. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises a N297G mutation. In some embodiments, the Fc comprises a N297Q mutation. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises a P329G mutation. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises G236A, A330S, and P331S mutations, which can be referred to as “GASDALIE” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises S239D and I332E mutations, which can be referred to as “SIE” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises S267E, H268F, S324T, and I332E mutations, which can be referred to as “SEHF_STIE” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises Y296W, T299A, and V308P mutations, which can be referred to as “YTEV” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises H310A, R409K, and Y435H mutations, which can be referred to as “HRY” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises T307A and T309A mutations, which can be referred to as “TATA” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises T307A and T309K mutations, which can be referred to as “TAKA” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises a K322A mutation. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises K326W and K334W mutations, which can be referred to as “WKWK” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises K326A and K334A mutations, which can be referred to as “AA” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises E234A, E235A, G237A, P238S, H268A, A330S, and P331S mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises T307A, E38OA, and N434A mutations, which can be referred to as “AAA” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises T250Q, and M428L mutations, which can be referred to as “QL” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises M428E, and N434S mutations, which can be referred to as “LS” mutations. In some embodiments, the Fc domain comprising Y296Q, F296Q, and / or P329K mutation, comprises M252Y, S254T, and T256E mutations, which can be referred to as “YTE” mutations.

[0059] Proteases

[0060] As used herein, "isotype" refers to the immunoglobulin class (e.g., IgGl, IgG2, IgG3, IgG4, IgM, IgAl, IgA2, IgD, and IgE antibody) that is encoded by the 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 cataloged in the UniProt database available on-line, e.g., as 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 of a heavy chain constant region, e.g., the hinge, is of an "IgGl isotype," "IgG2 isotype," "IgG3 isotype," or "IgG4 isotype," if the domain comprises the amino acid sequence of the corresponding domain of the respective isotype, or a variant thereof (that has a higher homology to the corresponding domain of the respective isotypc than it docs to that of the other isotypes).

[0061] “Allotype” refers to naturally occurring variants within a specific isotype group, which variants differ in a few amino acids (see, e.g., Jefferies et al. (2009) mAbs 1:1). Molecules described herein may be of any allotype.

[0062] A “wild-type” protein or portion thereof is a version of the protein as it is found in nature. An amino acid sequence of a wild-type protein, e.g., a heavy chain constant region, is the amino acid sequence of the protein as it occurs in nature. Due to allotypic differences, there can be more than one amino acid sequence for a wild-type protein. For example, there are several allotypes of naturally occurring human IGgl heavy chain constant regions (e.g., Jeffries et al. (2009) mAbs 1:1).

[0063] As used herein, the term “chemical liabilities” is meant to refer to factors that impact a molecule’s immunogenicity. Thus, in some embodiments, “chemical liabilities” is meant to refer to, without limitation, post-translational modifications, aggregation, glycosylation, impurities, or formulation components.

[0064] An immunoglobulin may be from any of the commonly known isotypes, including but not limited to IgA, secretory IgA, IgG and IgM. The IgG isotype is divided in 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, e.g., human IgGl, exist in several allotypes, which differ from each other in at most a few amino acids.

[0065] In some embodiments, the IgG proteins (hinge region underlined) are as provided in Table 2.

[0066] An "Fc region" (fragment crystallizable region) or "Fc polypeptide" or "Fc" refers to the C- terminal region of the heavy chain of an antibody that mediates the binding of the 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, an Fc region of an antibody of isotype IgG comprises the heavy chain constant region of the antibody excluding the first constant region immunoglobulin domain (CHI). In IgG, IgA and IgD antibody isotypes, the Fc region comprises CH2 and CH3 constant domains in each of the antibody’s two heavy chains; 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 immunoglobulin domains consisting of the hinge, CH2 and CH3. For purposes herein, the Fc region is defined as starting at amino acid 216 and ending at amino acid 447, wherein the numbering is 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 FIGs.3c-3f of U.S. Pat. App. Pub. No.2008 / 0248028. In some embodiments, the Fc region comprises the hinge region. The Fc may be a native (or naturally-occurring or wild-type) Fc, including any allotypic variant, or a 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 may comprise an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to a wild-type Fc. Modified or mutated Fes may have enhanced or reduced effector function and / or half-life. Fc may refer to this region in isolation or in the context of an Fc-comprising protein polypeptide such as a “binding protein comprising an Fc region,” also referred to as an “Fc fusion protein” (e.g., an antibody or immunoadhesin). In some embodiments, modified or variant Fc molecules have enhanced binding to FcyRIIb.

[0067] A "hinge", "hinge domain" or "hinge region" or "antibody hinge region" refers to the domain of a heavy chain constant region that joins the CHI domain to the CH2 domain and includes the upper, middle, and lower portions of the hinge (Roux et al. J. Immunol.1998 161:4083). The hinge provides varying levels of flexibility between the binding and effector regions of an antibody and also provides sites for intermolecular disulfide bonding between the two heavy chain constant regions. The term “hinge” includes wild-type hinges (such as those set forth in Table 3 of International Application No. PCT / US 2024 / 010503, filed January 5, 2024, which is hereby incorporated by reference in its entirety), as well as variants thereof (e.g., non- naturally-occurring hinges or modified hinges). For example, the term “IgGl hinge” includes wild-type IgGl hinge, as shown below, and variants having 1, 2, 3, 4, 5, 1-3, 1-5, 3-5 and / or at most 5, 4, 3, 2, or 1 mutations, e.g., substitutions, deletions or additions. In some embodiments, the hinge regions are as provided in Table 3.

[0068] The term “CHI domain” refers to the heavy chain constant region linking the variable domain to the hinge in a heavy chain constant domain. As used herein, a CHI domain includes wild type CHI domains, as well as variants thereof (e.g., non-naturally-occurring CHI domains or modified CHI domains). For example, the term “CHI domain” includes wild-type CHI domains and variants thereof having 1, 2, 3, 4, 5, 1-3, 1-5, 3-5 and / or at most 5, 4, 3, 2, or 1 mutations, e.g., substitutions, deletions or additions.

[0069] The term “CH2 domain” refers to the heavy chain constant region linking the hinge to the CH3 domain in a heavy chain constant domain. As used herein, a CH2 domain includes wildtype CH2 domains, as well as variants thereof (e.g., non-naturally-occumng CH2 domains or modified CH2 domains). For example, the term “CH2 domain” includes wild-type CH2 domains and variants thereof having 1, 2, 3, 4, 5, 1-3, 1-5, 3-5 and / or at most 5, 4, 3, 2, or 1 mutations, e.g., substitutions, deletions or additions.

[0070] The term “CH3 domain” refers to the heavy chain constant region that is C-terminus to the CH2 domain in a heavy chain constant domain. As used herein, a CH3 domain includes wildtype CH3 domains, as well as variants thereof (e.g., non-naturally- occurring CH3 domains or modified CH3 domains). For example, the term “CH3 domain” includes wild-type CH3 domains and variants thereof having 1, 2, 3, 4, 5, 1-3, 1-5, 3-5 and / or at most 5, 4, 3, 2, or 1 mutations, e.g., substitutions, deletions or additions.

[0071] Provided herein are variant Fc polypeptides comprising variant Fc polypeptides, e.g., Fc polypeptides that have a mutated sequence region, relative to wild-type Fc polypeptide. Exemplary variant Fc molecules comprising variant Fc polypeptides include an IgGl hinge, a CHI domain, a CH2 domain and a CH3 domain, wherein at least one of these constant domains has residues that are not wild-type residues, as compared to SEQ ID NO: 1, 2, 3, or 4. A variant Fc polypeptide may have effector function similar to that of wild-type IgG, or may be engineered to have enhanced effector function relative to that of the wild- type IgG. A variant Fc polypeptide may 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.

[0072] In some embodiments, the IgG proteins are as provided in Table 6.

[0073] In some embodiments, a variant Fc polypeptide comprises one or more mutations that confers resistance to recognition by a protease. In some embodiments, a variant Fc polypeptide comprises one or more mutations that confers resistance to proteolytic cleavage. In some embodiments, a variant Fc polypeptide comprises one or more mutations that confer resistance to recognition by a protease and proteolytic cleavage.

[0074] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence such as those provided in International Application Nos. PCT / US2023 / 080313, filed November 17, 2023, and PCT / US2024 / 010503, filed January 5, 2024, each of which is hereby incorporated by reference in its entirety.

[0075] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises an amino acid mutation at any one, or more, position between positions 234 and 329, as compared to SEQ ID NO: 1, wherein the mutation comprises an insertion, a deletion or a substitution.

[0076] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a mutation corresponding to L234A mutation, as compared to SEQ ID NO: 1.

[0077] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a mutation corresponding to L235A mutation, as compared to SEQ ID NO: 1.

[0078] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a mutation corresponding to G237A mutation, as compared to SEQ ID NO: 1. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a mutation corresponding to Y296Q mutation, as compared to SEQ ID NO: 1.

[0079] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a mutation corresponding to P329K mutation, as compared to SEQ ID NO: 1.

[0080] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, and G237A mutations, as compared to SEQ ID NO: 1.

[0081] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q and P329K mutations, as compared to SEQ ID NO: 1.

[0082] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, and P329K mutations, as compared to SEQ ID NO: 1. In some embodiments, a variant Fc polypeptide comprises a mutation set of L234A, L235A, G237A, Y296Q, and P329K as compared to SEQ ID NO: 1, wherein the variant 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: 1.

[0083] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to any sequence provided in Table 3 of International Application No. PCT / US2024 / 010503, filed January 5, 2024, which is hereby incorporated by reference in its entirety. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, 25, 42, 43, 44, 45, 46, 47, 48, or 49. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to:

[0084] DKTHTCPPCPAPEAAGAP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPREEQQNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL KAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHY TQKSLSLSPG ( SEQ ID NO : 23 ) .

[0085] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to any sequence provided in Table 3 of International Application No. PCT / US2024 / 010503, filed January 5, 2024, which is hereby incorporated by reference in its entirety, provided that the variant Fc polypeptide comprises one or more mutations at position 234, 235, 237, 265, 269, 296, 298, 329, or any combination thereof. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises one or more mutations at position 234, 235, 237, 265, 269, 296, 298, 329, or any combination thereof. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises one or more mutations at position 234, 235, 237, 265, 269, 296, 298, 329, or any combination thereof.

[0086] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to any sequence provided in Table 3 of International Application No. PCT / US2024 / 010503, filed January 5, 2024, which is hereby incorporated by reference in its entirety, and further comprises one or more mutations of L234A, L235A, G237A, Y296Q, P329K, or any combination thereof. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises one or more mutations of L234A, L235A, G237A, Y296Q, P329K, or any combination thereof. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises one or more mutations of L234A, L235A, G237A, Y296Q, P329K, or any combination thereof.

[0087] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, and P329K mutations. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, and P329K mutations.

[0088] In some embodiments, a valiant Fc polypeptide comprises a mutation set of L234A, L235A, G237A, Y296Q, and P329K as compared to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, wherein the variant 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 L234A, L235A, G237A, Y296Q, and P329K mutation set as compared to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25. In some embodiments, a valiant Fc polypeptide comprises a mutation set of L234A, L235A, G237A, Y296Q, and P329K as compared to SEQ ID NO: 23, wherein the variant 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 L234A, L235A, G237A, Y296Q, and P329K mutation set as compared to SEQ ID NO: 23.

[0089] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence as provided in Table 3 of International Application No. PCT / US2024 / 010503, filed January 5, 2024, which is hereby incorporated by reference in its entirety,. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 19, 20, 21, 22, 23, 24, 25, 42, 43, 44, 45, 46, 47, 48, or 49. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 19. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 20. In some embodiments, a valiant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 21. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 22. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 23. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 24. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 25. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 42. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 43. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 44. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 45. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 46. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 47. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 48. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 49.

[0090] In some embodiments, the valiant Fc polypeptide comprises at least one mutation that extends the half-life of the Fc polypeptide. In some embodiments, the at least one mutation that extends the half-life of the Fc polypeptide, is such as those known in the art and may be found in U.S. Patent Nos. 7,658,921, 11,059,892, or International Application No. PCT / US2008 / 088053, each of which is hereby incorporated by reference in its entirety. In some embodiments, the at least one mutation that extends the half-life of the Fc polypeptide, is such as those known in the art, such as, without limitation, a set of mutations of M428E and N434S (“LS” mutations), a set of mutations of M252Y, S254T, and T256E (“YTE” mutations), a set of mutations of E309D, Q311H, and N434Y, a set of mutations of E309D, Q311H, and N434S, a set of mutations of V309D, Q311H, and N434Y, or a set of mutations of V309D, Q311H, and N434S. The extension mutations can be combined with or used independently of the other Fc mutations provided for herein.

[0091] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, M428E and N434S mutations, as compared to SEQ ID NO: 1.

[0092] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, M252Y, S254T, and T256E mutations, as compared to SEQ ID NO: 1. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, L309D, Q311H, and N434Y mutations, as compared to SEQ ID NO: 1.

[0093] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, L309D, Q311H, and N434S mutations, as compared to SEQ ID NO: 1.

[0094] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, V309D, Q311H, and N434Y mutations, as compared to SEQ ID NO: 1.

[0095] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, V309D, Q311H, and N434S mutations, as compared to SEQ ID NO: 1.

[0096] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, M428L and N434S mutations, as compared to SEQ ID NO: 1. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, M252Y, S254T, and T256E mutations, as compared to SEQ ID NO: 1.

[0097] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, L309D, Q311H, and N434Y mutations, as compared to SEQ ID NO: 1.

[0098] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, L309D, Q311H, and N434S mutations, as compared to SEQ ID NO: 1.

[0099] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, V309D, Q311H, and N434Y mutations, as compared to SEQ ID NO: 1.

[0100] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, V309D, Q311H, and N434S mutations, as compared to SEQ ID NO: 1. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, M428L and N434S mutations, as compared to SEQ ID NO: 1.

[0101] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, M252Y, S254T, and T256E mutations, as compared to SEQ ID NO: 1.

[0102] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, L309D, Q311H, and N434Y mutations, as compared to SEQ ID NO: 1.

[0103] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, L309D, Q311H, and N434S mutations, as compared to SEQ ID NO: 1.

[0104] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, V309D, Q311H, and N434Y mutations, as compared to SEQ ID NO: 1. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, V309D, Q311H, and N434S mutations, as compared to SEQ ID NO: 1.

[0105] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, M428L and N434S mutations, as compared to SEQ ID NO: 1.

[0106] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, M252Y, S254T, and T256E mutations, as compared to SEQ ID NO: 1.

[0107] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, L309D, Q311H, and N434Y mutations, as compared to SEQ ID NO: 1.

[0108] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, L309D, Q311H, and N434S mutations, as compared to SEQ ID NO: 1. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, V309D, Q311H, and N434Y mutations, as compared to SEQ ID NO: 1.

[0109] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, V309D, Q311H, and N434S mutations, as compared to SEQ ID NO: 1.

[0110] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, M428L and N434S mutations, according to EU numbering.

[0111] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, M252Y, S254T, and T256E mutations, according to EU numbering.

[0112] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, L309D, Q311H, and N434Y mutations, according to EU numbering. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, L309D, Q311H, and N434S mutations, according to EU numbering.

[0113] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, V309D, Q311H, and N434Y mutations, according to EU numbering.

[0114] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, V309D, Q311H, and N434S mutations, according to EU numbering.

[0115] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, M428L and N434S mutations, according to EU numbering.

[0116] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, M252Y, S254T, and T256E mutations, according to EU numbering. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, L309D, Q311H, and N434Y mutations, according to EU numbering.

[0117] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, L309D, Q311H, and N434S mutations, according to EU numbering.

[0118] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, V309D, Q311H, and N434Y mutations, according to EU numbering.

[0119] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, V309D, Q311H, and N434S mutations, according to EU numbering.

[0120] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, M428L and N434S mutations, according to EU numbering. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, M252Y, S254T, and T256E mutations, according to EU numbering.

[0121] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, L309D, Q311H, and N434Y mutations, according to EU numbering.

[0122] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, L309D, Q311H, and N434S mutations, according to EU numbering.

[0123] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, V309D, Q311H, and N434Y mutations, according to EU numbering.

[0124] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, V309D, Q311H, and N434S mutations, according to EU numbering. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, M428L and N434S mutations, according to EU numbering.

[0125] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, M252Y, S254T, and T256E mutations, according to EU numbering.

[0126] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, L309D, Q311H, and N434Y mutations, according to EU numbering.

[0127] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, L309D, Q311H, and N434S mutations, according to EU numbering.

[0128] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, V309D, Q311H, and N434Y mutations, according to EU numbering. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 1395, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, V309D, Q311H, and N434S mutations, according to EU numbering.

[0129] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, M428L and N434S mutations, according to EU numbering.

[0130] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, M252Y, S254T, and T256E mutations, according to EU numbering.

[0131] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, L309D, Q311H, and N434Y mutations, according to EU numbering.

[0132] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, L309D, Q311H, and N434S mutations, according to EU numbering. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, V309D, Q311H, and N434Y mutations, according to EU numbering.

[0133] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, V309D, Q311H, and N434S mutations, according to EU numbering.

[0134] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, M428L and N434S mutations, according to EU numbering.

[0135] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, M252Y, S254T, and T256E mutations, according to EU numbering.

[0136] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, L309D, Q311H, and N434Y mutations, according to EU numbering. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, L309D, Q311H, and N434S mutations, according to EU numbering.

[0137] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, V309D, Q311H, and N434Y mutations, according to EU numbering.

[0138] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, V309D, Q311H, and N434S mutations, according to EU numbering.

[0139] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, M428L and N434S mutations, according to EU numbering.

[0140] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, M252Y, S254T, and T256E mutations, according to EU numbering. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, L309D, Q311H, and N434Y mutations, according to EU numbering.

[0141] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, L309D, Q311H, and N434S mutations, according to EU numbering.

[0142] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, V309D, Q311H, and N434Y mutations, according to EU numbering.

[0143] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, V309D, Q311H, and N434S mutations, according to EU numbering.

[0144] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, M428L and N434S mutations, according to EU numbering. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, M252Y, S254T, and T256E mutations, according to EU numbering.

[0145] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, L309D, Q311H, and N434Y mutations, according to EU numbering.

[0146] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, L309D, Q311H, and N434S mutations, according to EU numbering.

[0147] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21, 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, V309D, Q311H, and N434Y mutations, according to EU numbering.

[0148] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 19, 20, 21 , 22, 23, 24, or 25, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, V309D, Q311H, and N434S mutations, according to EU numbering.

[0149] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, M428L and N434S mutations, according to EU numbering.

[0150] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, M252Y, S254T, and T256E mutations, according to EU numbering.

[0151] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, L309D, Q311H, and N434Y mutations, according to EU numbering.

[0152] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, L309D, Q311H, and N434S mutations, according to EU numbering.

[0153] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, V309D, Q311H, and N434Y mutations, according to EU numbering.

[0154] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, V309D, Q311H, and N434S mutations, according to EU numbering.

[0155] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, M428L and N434S mutations, according to EU numbering.

[0156] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, M252Y, S254T, and T256E mutations, according to EU numbering.

[0157] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, L309D, Q311H, and N434Y mutations, according to EU numbering.

[0158] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, L309D, Q31 1 H, and N434S mutations, according to EU numbering.

[0159] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, V309D, Q311H, and N434Y mutations, according to EU numbering.

[0160] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to P329K, V309D, Q311H, and N434S mutations, according to EU numbering.

[0161] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, M428L and N434S mutations, according to EU numbering.

[0162] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, M252Y, S254T, and T256E mutations, according to EU numbering.

[0163] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, L309D, Q31 1 H, and N434Y mutations, according to EU numbering.

[0164] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, L309D, Q311H, and N434S mutations, according to EU numbering.

[0165] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, V309D, Q311H, and N434Y mutations, according to EU numbering.

[0166] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to Y296Q, P329K, V309D, Q311H, and N434S mutations, according to EU numbering.

[0167] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, M428L and N434S mutations, according to EU numbering.

[0168] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, M252Y, S254T, and T256E mutations, according to EU numbering.

[0169] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, L309D, Q311H, and N434Y mutations, according to EU numbering.

[0170] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, L309D, Q311H, and N434S mutations, according to EU numbering.

[0171] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, V309D, Q311H, and N434Y mutations, according to EU numbering.

[0172] In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 23, provided that the variant Fc polypeptide comprises a set of mutations corresponding to L234A, L235A, G237A, Y296Q, P329K, V309D, Q311H, and N434S mutations, according to EU numbering.

[0173] The mutations and positions of the Fc polypeptide, which can also be referred to as the Fc polypeptide, are according to EU numbering.

[0174] As used herein, a Fc polypeptide / domain comprising a mutation at a specific position is as compared to the wild-type Fc according the numbering system (EU numbering) as referenced herein. In some embodiments, a variant Fc polypeptide comprises an amino acid sequence having a C-tcrminal lysine (K). In some embodiments, a variant Fc polypeptide comprises an amino acid sequence not having a C-terminal lysine (K).

[0175] In some embodiments, the variant Fc polypeptide, such as those provided herein, is conjugated to another polypeptide. In some embodiments, the another polypeptide is an antibody. In some embodiments, the variant Fc polypeptide, such as those provided herein, is conjugated to an effector binding / modulating polypeptide or a tissue targeting polypeptide. In some embodiments, the variant Fc polypeptide, such as those provided herein, is conjugated to an antibody, or antigen-binding fragment thereof. In some embodiments, the variant Fc polypeptide, such as those, is conjugated to another polypeptide via a linker or a covalent bond. In some embodiments, the linker is a protein linker, such as those provided herein.

[0176] The present disclosure provides for polypeptides, molecules, compounds, therapeutics, and compositions comprising a polypeptide having protease activity, which can be covalently or non-covalently connected to a Fc polypeptide domain, such as those provided for herein. In some embodiments, the polypeptide having protease activity is an IgG protease. In some embodiments, the polypeptide having protease activity is IdeS, IdeSsuis, IdeZ, IdeE, IdeE2, IdeZ2, or IdeC.

[0177] Streptococcus pyogenes is a significant bacterial pathogen that secretes two enzymes showing remarkable specificity for IgG; EndoS and IdeS. EndoS (Endoglycosidase in Streptococcus pyogenes) specifically hydrolyzes the functionally important N-linked glycan of IgG, and treatment with EndoS abrogates the pathogenic activity of IgG in mouse models of autoimmune disease. (Collin M, Olsen A. EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG. Embo J. 2001;20:3046-3055; Nandakumar KS, Collin M, Olsen A, Nimmerjahn F, Blom AM, et al. Endoglycosidase treatment abrogates IgG arthritogenicity: importance of IgG glycosylation in arthritis. Eur J Immunol. 2007;37:2973-2982) IdeS (Immunoglobulin G-degrading enzyme of Streptococcus pyogenes) is a cysteine proteinase which cleaves IgG with a unique degree of specificity in the hinge region. (Wenig K, Chatwell L, von Pawel-Rammlngen U, Bjbrck L, Huber R, et al. Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG. Proc Natl Acad Sci USA. 2004;101:17371-17376) IdeS is extremely specific for IgG, which is hydrolyzed in the hinge region after glycine residue 236 in both heavy chains, which generates one F(ab')2 and two monomeric Fc fragments. IdeE is a homolog of the secreted IgG- specific protease IdeS / Mac of Streptococcus pyogenes. The activity of IdeE is comparable with the activity of IdcZ, the corresponding enzyme of the closely related 5. equi ssp. zooepidemicus .

[0178] The full sequence of IdeS is publicly available as NCBI Reference Sequence no.

[0179] WP_010922160.1 and is provided herein as SEQ ID NO: 35:

[0180] MRKRCYSTSAAVLAAVTLFVLSVDRGVIADSFSANQEIRYSEVTPYHVTSVWTKGVTPP ANFTQGEDVFHAPYVANQGWYDITKTFNGKDDLLCGAATAGNMLHWWFDQNKDQIKRYL EEHPEKQKINFNGEQMFDVKEAIDTKNHQLDSKLFEYFKEKAFPYLSTKHLGVFPDHVI DMFINGYRLSLTNHGPTPVKEGSKDPRGGIFDAVFTRGDQSKLLTSRHDFKEKNLKEIS DLIKKELTEGKALGLSHTYANVRINHVINLWGADFDSNGNLKAIYVTDSDSNASIGMKK YFVGVNSAGKVAISAKEIKEDNIGAQVLGLFTLSTGQDSWNQTN ( SEQ ID NO : 35 ) .

[0181] This sequence includes an N-terminus methionine followed by a 28 amino acid secretion signal sequence. The N-terminus methionine and the signal sequence (a total of 29 amino acids at the N terminus) are typically removed to form the mature IdeS protein, the amino acid sequence of which is publicly available as UniProt Identifier Q9F1R7_STRPY and is provided herein as SEQ ID NO: 36. Another valiant of an IdeS protease that can be used as a reference sequence can be as illustrated in SEQ ID NO: 1349, which is similar to the amino acid sequence of SEQ ID NO: 36, but has an additional 4 amino acid residues at the N-terminus, which are DSFS (SEQ ID NO: 1350).

[0182] IdeZ is an IgG cysteine protease produced by Streptococcus equi ssp. zooepidemicus, a bacterium predominantly found in horses. As IdeZ is not a human pathogen, human subjects do not typically have antibodies against this protein in their plasma. However, IdeZ has a level of IgG cysteine protease activity against human IgG which is considerably lower than that of IdeS. The full sequence of IdeZ is publicly available as UniProt Identifier QOPIW 1 and is provided herein as SEQ ID NO: 1331 below:

[0183] MKTIAYPNKPHSLSAGLLTAIAIFSLASSNITYADDYQRNAAEVYAKEVPHQIT SVWTKGVTPLTPEQFRYNNEDVIHAPYLAHQGWYDITKVFDGKDNLLCGAATAG NMLHWWFDQNKTEIEAYLSKHPEKQKI IFNNQELFDLKAAIDTKDSQTNSQLFN YFRDKAFPNLSARQLGVMPDLVLDMFINGYYLNVFKTQSTDVNRPYQDKDKRGG IFDAVFTRGDQTTLLTARHDLKNKGLNDISTI IKQELTEGRALALSHTYANVSI SHVINLWGADFNAEGNLEAIYVTDSDANASIGMKKYFVGINAHGHVAISAKKIE GENIGAQVLGLFTLSSGKDIWQKLS (SEQ ID NO: 1331).

[0184] In some embodiments, IdeZ is publicly available as NCBI Reference Sequence no WP_014622780.1 and is provided herein as SEQ ID NO: 1332 below: MKTIAYPNKPHSLSAGLLTAIAIFSLASSNITYADDYQRNATEAYAKEVPHQIT SVWTKGVIPLIPEQFRYNNEDVIHAPYLAHQGWYDITKAFDGKDNLLCGAATAG NMLHWWFDQNKTEIEAYLSKHPEKQKI IFNNQELFDLKAAIDTKDSQINSQLFN YFRDKAFPNLSARQLGVMPDLVLDMFINGYYLNVFKIQSTDVNRPYQDKDKRGG IFDAVFIRGDQTILLTARHDLKNKGLNDISTI IKQELTEGRALALSHIYANVSI SHVINLWGADFNAEGNLEAIYVIDSDANASIGMKKYFVGINAHGHVAISAKKIE GENIGAQVLGLFTLSSGKDIWQKLS (SEQ ID NO: 1332).

[0185] The mature sequence of IdeZ is publicly available as UniProt Identifier A0A0D0YKS5_STRSZ and is provided herein as SEQ ID NO: 38.

[0186] In some embodiments, the polypeptide having protease activity is IdeS, IdeSsuis, IdeZ, IdeE, IdeE2, IdeZ2, Ide85, or IdeC. In some embodiments, the IdeS, IdeZ, IdeE, IdeE2, IdeZ2, Ide85, or IdeC protease has an amino acid sequence such as those provided herein. The mature sequence of IdeSsuis is publicly available as UniProt Identifier C5W022 and is provided herein as SEQ ID NO: 55. The mature sequence of IdeE is publicly available as UniProt Identifier C0M8U6_STRE4 and is provided herein as SEQ ID NO: 37. The mature sequence of IdeE2 is publicly available as UniProt Identifier C7B615_9STRE and is provided herein as SEQ ID NO: 39. The mature sequence of IdeZ2 is publicly available as UniProt Identifier B4U2F7_STREM and is provided herein as SEQ ID NO: 40. The mature sequence of IdeC is publicly available as UniProt Identifier A0A3P5YAY8_STRCB and is provided herein as SEQ ID NO: 41. In some embodiments, the protease is an IgG degrading protease. In some embodiments, the protease is an IgM degrading protease.

[0187] In some embodiments, a polypeptide having protease activity comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to any sequence provided in Table 4 of International Application No. PCT / US2024 / 010503, filed January 5, 2024, which is hereby incorporated by reference in its entirety. In some embodiments, the polypeptide having protease activity is IdeS. In some embodiments, the polypeptide having protease activity is IdeSsuis. In some embodiments, the polypeptide having protease activity is IdeE. In some embodiments, the polypeptide having protease activity is IdeZ. In some embodiments, the polypeptide having protease activity is IdeE2. In some embodiments, the polypeptide having protease activity is IdeZ2. In some embodiments, the polypeptide having protease activity is Ide85. In some embodiments, the polypeptide having protease activity is IdeC. In some embodiments, a polypeptide having protease activity comprises an amino acid sequence having at least 50%, 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%, or 100% sequence identity to SEQ ID NO: 26, 28, 29, 31, 36, 37, 38, 39, 40, 41, 50, 51, 52, or 55.

[0188] In some embodiments, a polypeptide having protease activity comprises an amino acid sequence such as those provided in U.S. Patent No. 7,666,582, issued February 23, 2010, 8,133,483, issued March 13, 2012, 10,973,889, issued April 13, 2021, 10,696,959, issued June 30, 2020, 11,214,784, issued January 4, 2022, 11,667,905, issued June 6, 2023, 10,758,597, issued August 1, 2020, 11,524,057, issued December 13, 2022, U.S. Publication Nos. 20230302100, filed November 8, 2022, 20230357741, filed May 16, 2023, 20230302100, filed November 8, 2022, 20240360432, filed November 18, 2022, International Application Nos. PCT / US2024 / 048126, filed September 24, 2024, PCT / US2024 / 040614, filed August 1, 2024, PCT / US2024 / 022411, filed March 29, 2024, PCT / US2024 / 019042, filed March 8, 2024, PCT / US2024 / 010503, filed January 5, 2024, PCT / US2023 / 080313, filed November 17, 2023, PCT / US2023 / 068902, filed June 22, 2023, PCT / IB2023 / 052463, filed March 14, 2023, PCT / CN2022 / 141001, filed December 22, 2022, and PCT / US2020 / 046809, filed August 18, 2020, each of which is hereby incorporated by reference in its entirety.

[0189] In some embodiments, the protease comprises an amino acid sequence that comprises a signal sequence. In some embodiments, the protease comprises an amino acid sequence that does not comprise a signal sequence. In some embodiments, the signal sequence can have the amino acid sequence of METDTLLLWVLLLWVPGSTG (SEQ ID NO: 53), or MNIQERFSLRKSAVGLVSVSLLCAIYTSTVAA (SEQ ID NO: 54).

[0190] In some embodiments, the protease has an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one amino acid sequence selected from SEQ ID NO: 55-1019, 1290- 1310 and 1333. Additional support for specific embodiments of proteases having an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one amino acid sequence selected from SEQ ID NO: 55-1019, 1290-1310 and 1333 may be found in U.S. Provisional Application No. 63 / 478,789, filed January 6, 2023, U.S. Provisional Application No. 63 / 483,142, filed February 3, 2023, U.S. Provisional Application No. 63 / 493,142, filed March 31, 2023, U.S. Provisional Application No. 63 / 506,539, filed June 6, 2023, and / or U.S. Provisional Application No.

[0191] 63 / 600,157, filed November 17, 2023, U.S. Non-Provisional Application No. 18 / 405,861, filed January 5, 2024, now U.S. Patent No. 12,129,499, issued October 29, 2024, U.S. NonProvisional Application No. 18 / 885,268, filed September 13, 2024, and International Application Nos. PCT / US2024 / 010503, filed January 5, 2024, each of which is hereby incorporated by reference in its entirety.

[0192] In some embodiments, the protease has an amino acid sequence selected from SEQ ID NO: 55-1019, 1290-1310 and 1333.

[0193] In some embodiments, the protease has an amino acid sequence of:

[0194] VTSVWTKGVTPPTDFIYGEDVLHAPYKAGQGWYDITKLFNGKDDLLCGAATAGNMLHWWFDQNKE QIKNYLKKYPEKQKINFGGEQLFDVKEAIDTKDSQLDSKLFDYFKEKAFPYLSTKHLGVFPDHVI DMFINGYRLSLTDHGPTPVKRGSKDPRGGIFDAVFTRGDQSKLLTNRYDLKEKTLKEI SDLIKQE LTEGKALGISHTYANVRIGHVINLWGADFDAEGNLEAIYVTDSDSNPSIGMKKYFVGVNSSGKVA I SAKEIEEDNIGAQVLGLFTLSTGQDIWNQTN (SEQ ID NO: 1303).

[0195] In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 56. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 57. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 58. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 59. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 60. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 61. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 62. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 63. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 64. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 65. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 66. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 67. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 68. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 69. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 70. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 71. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 72. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 73. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 74. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 75. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 76. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 77. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 78. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 79. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 80. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 81. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 82. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 83. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 84. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 85. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 86. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 87. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 88. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 89. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 90. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 91. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 92. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 93. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 94. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 95. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 96. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 97. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 98. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 99. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 100. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 101. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 102. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 103. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 104. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 105. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 106. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 107. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 108. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 109. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 110. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 111. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 112. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 113. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 114. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 115. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 116. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 117. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 118. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 119. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 120. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 121. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 122. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 123. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 124. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 125. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 126. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 127. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 128. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 129. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 130. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 131. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 132. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 133. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 134. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 135. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 136. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 137. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 138. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 139. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 140. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 141. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 142. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 143. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 144. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 145. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 146. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 147. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 148. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 149. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 150. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 151. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 152. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 153. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 154. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 155. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 156. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 157. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 158. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 159. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 160. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 161. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 162. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 163. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 164. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 165. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 166. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 167. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 168. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 169. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 170. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 171. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 172. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 173. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 174. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 175. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 176. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 177. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 178. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 179. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 180. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 181. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 182. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 183. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 184. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 185. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 186. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 187. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 188. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 189. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 190. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 191. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 192. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 193. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 194. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 195. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 196. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 197. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 198. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 199. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 200. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 201. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 202. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 203. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 204. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 205. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 206. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 207. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 208. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 209. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 210. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 211. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 212. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 213. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 214. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 215. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 216. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 217. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 218. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 219. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 220. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 221. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 222. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 223. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 224. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 225. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 226. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 227. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 228. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 229. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 230. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 231. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 232. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 233. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 234. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 235. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 236. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 237. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 238. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 239. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 240. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 241. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 242. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 243. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 244. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 245. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 246. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 247. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 248. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 249. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 250. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 251. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 252. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 253. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 254. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 255. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 256. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 257. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 258. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 259. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 260. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 261. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 262. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 263. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 264. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 265. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 266. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 267. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 268. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 269. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 270. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 271. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 272. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 273. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 27 . In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 275. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 276. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 277. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 278. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 279. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 280. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 281. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 282. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 283. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 284. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 285. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 286. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 287. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 288. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 289. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 290. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 291. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 292. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 293. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 294. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 295. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 296. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 297. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 298. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 299. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 300. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 301. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 302. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 303. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 304. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 305. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 306. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 307. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 308. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 309. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 310. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 311. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 312. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 313. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 314. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 315. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 316. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 317. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 318. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 319. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 320. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 321. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 322. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 323. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 324. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 325. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 326. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 327. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 328. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 329. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 330. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 331. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 332. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 333. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 334. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 335. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 336. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 337. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 338. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 339. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 340. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 341. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 342. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 343. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 344. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 345. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 346. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 347. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 348. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 349. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 350. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 351 . In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 352. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 353. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 354. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 355. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 356. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 357. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 358. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 359. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 360. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 361. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 362. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 363. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 364. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 365. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 366. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 367. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 368. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 369. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 370. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 371. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 372. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 373. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 374. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 375. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 376. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 377. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 378. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 379. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 380. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 381. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 382. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 383. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 384. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 385. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 386. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 387. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 388. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 389. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 390. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 391. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 392. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 393. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 394. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 395. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 396. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 397. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 398. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 399. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 400. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 401. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 402. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 403. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 404. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 405. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 406. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 407. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 408. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 409. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 410. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 411. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 412. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 413. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 414. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 415. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 416. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 417. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 418. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 419. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 420. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 421. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 422. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 423. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 424. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 425. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 426. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 427. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 428. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 429. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 430. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 431. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 432. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 433. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 434. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 435. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 436. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 437. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 438. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 439. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 440. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 441. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 442. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 443. In some

[0196] -I l l- embodiments, the protease has an amino acid sequence of SEQ ID NO: 444. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 445. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 446. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 447. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 448. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 449. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 450. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 451. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 452. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 453. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 454. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 455. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 456. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 457. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 458. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 459. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 460. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 461. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 462. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 463. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 464. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 465. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 466. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 467. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 468. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 469. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 470. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 471. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 472. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 473. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 474. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 475. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 476. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 477. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 478. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 479. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 480. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 481. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 482. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 483. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 484. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 485. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 486. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 487. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 488. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 489. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 490. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 491. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 492. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 493. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 494. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 495. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 496. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 497. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 498. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 499. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 500. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 501. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 502. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 503. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 504. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 505. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 506. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 507. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 508. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 509. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 510. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 511. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 512. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 513. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 514. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 515. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 516. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 517. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 518. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 519. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 520. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 521. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 522. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 523. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 524. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 525. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 526. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 527. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 528. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 529. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 530. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 531. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 532. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 533. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 534. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 535. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 536. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 537. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 538. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 539. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 540. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 5 1. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 542. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 543. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 544. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 545. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 546. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 547. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 548. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 549. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 550. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 551. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 552. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 553. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 554. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 555. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 556. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 557. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 558. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 559. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 560. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 561. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 562. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 563. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 564. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 565. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 566. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 567. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 568. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 569. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 570. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 571. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 572. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 573. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 574. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 575. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 576. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 577. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 578. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 579. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 580. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 581. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 582. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 583. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 584. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 585. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 586. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 587. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 588. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 589. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 590. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 591. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 592. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 593. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 594. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 595. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 596. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 597. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 598. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 599. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 600. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 601. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 602. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 603. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 604. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 605. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 606. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 607. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 608. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 609. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 610. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 611. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 612. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 613. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 61 . In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 615. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 616. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 617. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 618. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 619. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 620. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 621. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 622. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 623. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 624. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 625. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 626. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 627. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 628. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 629. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 630. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 631. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 632. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 633. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 634. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 635. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 636. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 637. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 638. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 639. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 640. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 641. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 642. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 643. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 644. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 645. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 646. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 647. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 648. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 649. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 650. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 651. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 652. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 653. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 654. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 655. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 656. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 657. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 658. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 659. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 660. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 661 . In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 662. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 663. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 664. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 665. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 666. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 667. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 668. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 669. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 670. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 671. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 672. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 673. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 67 . In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 675. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 676. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 677. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 678. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 679. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 680. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 681. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 682. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 683. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 684. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 685. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 686. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 687. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 688. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 689. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 690. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 691. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 692. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 693. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 694. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 695. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 696. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 697. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 698. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 699. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 700. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 701. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 702. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 703. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 704. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 705. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 706. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 707. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 708. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 709. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 710. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 711. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 712. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 713. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 714. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 715. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 716. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 717. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 718. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 719. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 720. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 721. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 722. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 723. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 724. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 725. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 726. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 727. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 728. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 729. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 730. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 731. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 732. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 733. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 734. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 735. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 736. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 737. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 738. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 739. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 740. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 741. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 742. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 743. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 744. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 745. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 746. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 747. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 748. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 749. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 750. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 751. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 752. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 753. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 754. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 755. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 756. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 757. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 758. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 759. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 760. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 761. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 762. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 763. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 764. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 765. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 766. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 767. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 768. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 769. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 770. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 771. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 772. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 773. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 774. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 775. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 776. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 777. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 778. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 779. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 780. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 781. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 782. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 783. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 784. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 785. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 786. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 787. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 788. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 789. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 790. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 791. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 792. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 793. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 794. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 795. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 796. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 797. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 798. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 799. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 800. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 801. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 802. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 803. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 804. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 805. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 806. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 807. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 808. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 809. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 810. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 811. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 812. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 813. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 814. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 815. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 816. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 817. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 818. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 819. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 820. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 821. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 822. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 823. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 824. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 825. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 826. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 827. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 828. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 829. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 830. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 831. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 832. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 833. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 834. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 835. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 836. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 837. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 838. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 839. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 840. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 841. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 842. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 843. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 844. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 845. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 846. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 847. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 848. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 849. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 850. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 851. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 852. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 853. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 854. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 855. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 856. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 857. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 858. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 859. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 860. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 861. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 862. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 863. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 864. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 865. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 866. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 867. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 868. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 869. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 870. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 871. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 872. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 873. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 874. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 875. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 876. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 877. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 878. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 879. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 880. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 881. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 882. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 883. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 884. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 885. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 886. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 887. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 888. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 889. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 890. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 891. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 892. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 893. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 894. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 895. In some embodiments, the protease has an amino acid sequence of SEQ ID NO: 896. ...

Claims

1. What is claimed:

1. A method of treating a disease or a disorder in a subject in need thereof, the method comprising administering to the subject:(a) an IgG protease; and(b) an enzyme replacement therapy (ERT), or a therapeutic antibody, wherein: the ERT is a recombinant enzyme linked to an Fc domain comprising a mutation, or a set of mutations of Y296Q, F296Q, and / or P329K according to EU numbering, and the therapeutic antibody comprises an IgG heavy chain Fc domain comprising a mutation, or a set of mutations of Y296Q, F296Q, and / or P329K in the Fc domain of the heavy chain, according to EU numbering.

2. The method of claim 1, wherein the IgG protease comprises an amino acid sequence having at least 50% sequence identity to any one of SEQ ID NO: 1303, 1290, 1291, 1292, 1293, 1294, 1295, 1296, 1297, 1298, 1299, 1300, 1301, 1302, 1304, 1305, 1306, 1307, 1308, 1309, 1310, and 1333, provided that the polypeptide comprises any one of, or any combination of, a threonine (T) at position 60, an aspartic acid (D) at position 61, an isoleucine (I) at position 63, a tyrosine (Y) at position 64, a leucine (L) at position 69, a lysine (K) at position 74, a glycine (G) at position 76, a leucine (L) at position 85, a glutamic acid (E) at position 112, a glutamic acid (E) at position 115, an asparagine (N) at position 116, a lysine (K) at position 119, a lysine (K) at position 120, a tyrosine (Y) at position 121, a lysine (K) at position 130, a glycine (G) at position 130, a leucine (L) at position 134, an aspartic acid (D) at position 145, a serine (S) at position 146, an aspartic acid (D) at position 154, an aspartic acid (D) at position 190, an arginine (R) at position 198, an asparagine (N) at position 223, a tyrosine (Y) at position 225, a leucine (L) at position 227, a threonine (T) at position 231, a glutamine (Q) at position 241, an isoleucine (I) at position 251, a glycine (G) at position 261, an alanine (A) at position 273, a glutamic acid (E) at position 274, a glutamic acid (E) at position 278, an asparagine (N) at position 286, a proline (P) at position 289, a serine (S) at position 303, a glutamic acid (E) at position 314, an isoleucine (I) at position 334, and glutamine (Q) at position 336, as compared to SEQ ID NO: 35.

3. The method of claim 1 , wherein the therapeutic antibody is Rituxan (rituximab), Ocrevus (ocrclizumab), Orcncia (abataccpt), Stelara (ustckinumab), Coscntyx (sccukinumab), Trcmfya (guselkumab), Skyrizi (risankizumab), Dupixent (dupilumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Tysabri (natalizumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Taltz (ixekizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Prolia (denosumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab- CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Haris (canakinumab), Arcalyst (rilonacept), Omvoh (mirikizumab), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spevigo (spesolimab), Cinqair (reslizumab), Kevzara (sarilumab), Sylvant (siltuximab), Adbry (tralokinumab), or Ebglyss (lebrikizumab).

4. The method of claim 2, wherein the IgG protease comprises: a threonine (T) at position 60, an aspartic acid (D) at position 61, an isoleucine (I) at position 63, a tyrosine (Y) at position 64, a leucine (L) at position 69, a lysine (K) at position 74, a glycine (G) at position 76, a leucine (L) at position 85, a glutamic acid (E) at position 112, a glutamic acid (E) at position 115, an asparagine (N) at position 116, a lysine (K) at position 119, a lysine (K) at position 120, a tyrosine (Y) at position 121, a lysine (K) at position 130, a leucine (L) at position 134, an aspartic acid (D) at position 145, a serine (S) at position 146, an aspartic acid (D) at position 154, an aspartic acid (D) at position 190, an arginine (R) at position 198, an asparagine (N) at position 223, a tyrosine (Y) at position 225, a leucine (L) at position 227, a threonine (T) at position 231, a glutamine (Q) at position 241, an isoleucine (I) at position 251, an alanine (A) at position 273, a glutamic acid (E) at position 274, a glutamic acid (E) at position 278, a proline (P) at position 289, a serine (S) at position 303, a glutamic acid (E) at position 314, an isoleucine (I) at position 334, and a glutamine (Q) at position 336, as compared to SEQ ID NO: 35; a threonine (T) at position 60, an aspartic acid (D) at position 61, an isoleucine (I) at position 63, a tyrosine (Y) at position 64, a leucine (L) at position 69, a lysine (K) at position 74, a glycine (G) at position 76, a leucine (L) at position 85, a glutamic acid (E)at position 112, a glutamic acid (E) at position 115, an asparagine (N) at position 116, a lysine (K) at position 119, a lysine (K) at position 120, a tyrosine (Y) at position 121, a lysine (K) at position 130, a leucine (L) at position 134, an aspartic acid (D) at position145, a serine (S) at position 146, an aspartic acid (D) at position 154, an aspartic acid (D) at position 190, an arginine (R) at position 198, an asparagine (N) at position 223, a tyrosine (Y) at position 225, a leucine (L) at position 227, a threonine (T) at position 231, a glutamine (Q) at position 241, an isoleucine (I) at position 251, a glycine (G) at position 258, an alanine (A) at position 273, a glutamic acid (E) at position 274, a glutamic acid (E) at position 278, a proline (P) at position 289, a serine (S) at position 303, a glutamic acid (E) at position 314, an isoleucine (I) at position 334, and a glutamine (Q) at position 336, as compared to SEQ ID NO: 35; a threonine (T) at position 60, an aspartic acid (D) at position 61, an isoleucine (I) at position 63, a tyrosine (Y) at position 64, a leucine (L) at position 69, a lysine (K) at position 74, a glycine (G) at position 76, a leucine (L) at position 85, a glutamic acid (E) at position 112, a glutamic acid (E) at position 115, an asparagine (N) at position 116, a lysine (K) at position 119, a lysine (K) at position 120, a tyrosine (Y) at position 121, a leucine (L) at position 134, an aspartic acid (D) at position 145, a serine (S) at position146, an aspartic acid (D) at position 154, an aspartic acid (D) at position 190, an arginine (R) at position 198, an asparagine (N) at position 223, a tyrosine (Y) at position 225, a leucine (L) at position 227, a threonine (T) at position 231, a glutamine (Q) at position 241, an isoleucine (I) at position 251, an alanine (A) at position 273, a glutamic acid (E) at position 274, a glutamic acid (E) at position 278, an asparagine (N) at position 286, a proline (P) at position 289, a serine (S) at position 303, a glutamic acid (E) at position 314, an isoleucine (I) at position 334, and a glutamine (Q) at position 336, as compared to SEQ ID NO: 35; a threonine (T) at position 60, an aspartic acid (D) at position 61, an isoleucine (I) at position 63, a tyrosine (Y) at position 64, a leucine (L) at position 69, a lysine (K) at position 74, a glycine (G) at position 76, a leucine (L) at position 85, a glutamic acid (E) at position 112, an asparagine (N) at position 116, a lysine (K) at position 119, a lysine(K) at position 120, a tyrosine (Y) at position 121, a glycine (G) at position 130, a leucine(L) at position 134, an aspartic acid (D) at position 145, a serine (S) at position 146, anaspartic acid (D) at position 154, an aspartic acid (D) at position 190, an arginine (R) at position 198, an asparagine (N) at position 223, a tyrosine (Y) at position 225, a leucine (L) at position 227, a threonine (T) at position 231, a glutamine (Q) at position 241, an isoleucine (I) at position 251, a glycine (G) at position 261, an alanine (A) at position 273, a glutamic acid (E) at position 274, a glutamic acid (E) at position 278, a proline (P) at position 289, a serine (S) at position 303, a glutamic acid (E) at position 314, and an isoleucine (I) at position 334, as compared to SEQ ID NO: 35; or a threonine (T) at position 60, an aspartic acid (D) at position 61, an isoleucine (I) at position 63, a tyrosine (Y) at position 64, a leucine (L) at position 69, a lysine (K) at position 74, a glycine (G) at position 76, a leucine (L) at position 85, a glutamic acid (E) at position 112, a glutamic acid (E) at position 115, an asparagine (N) at position 116, a lysine (K) at position 119, a lysine (K) at position 120, a tyrosine (Y) at position 121, a lysine (K) at position 130, a leucine (L) at position 134, an aspartic acid (D) at position 145, a serine (S) at position 146, an aspartic acid (D) at position 154, an aspartic acid (D) at position 190, an arginine (R) at position 198, an asparagine (N) at position 223, a tyrosine (Y) at position 225, a leucine (L) at position 227, a threonine (T) at position 231, a glutamine (Q) at position 241, an isoleucine (I) at position 251, a glycine (G) at position 261, an alanine (A) at position 273, a glutamic acid (E) at position 274, a glutamic acid (E) at position 278, a proline (P) at position 289, a serine (S) at position 303, a glutamic acid (E) at position 314, an isoleucine (I) at position 334, and a glutamine (Q) at position 336, as compared to SEQ ID NO: 35.

5. The method of claim 2, wherein the IgG protease comprises a cysteine (C) at position 94; and / or has, at the positions in said variant sequence which correspond to positions 84, 262, 284 and 286 of SEQ ID NO: 35, a lysine (K), a histidine (H), an aspartic acid (D) and / or an aspartic acid (D), respectively.

6. The method of any one of claims 1-5, wherein the IgG protease further comprises: a positively charged amino acid at a position 130, optionally wherein said positively charged amino acid is arginine (R) or lysine (K); and / ora positively charged amino acid at a position 131 , optionally wherein said positively charged amino acid is arginine (R) or lysine (K).

7. The method of any one of claims 1-6, wherein the IgG protease is less immunogenic than a wild- type IdeS.

8. The method of any one of claims 1-7, wherein the IgG protease comprises an amino acid sequence of any one of SEQ ID NOs: 1303, 1290, 1291, 1292, 1293, 1294, 1295, 1296, 1297, 1298, 1299, 1300, 1301, 1302, 1304, 1305, 1306, 1307, 1308, 1309, 1310, and 1333.

9. The method of any one of claims 1-8, wherein the IgG protease is covalently or non- covalently conjugated to an Fc polypeptide.

10. The method of claim 9, wherein the Fc polypeptide comprises an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 19, 20, 21, 22, 23, 24, or 25.

11. The method of claim 10, wherein the Fc polypeptide comprises an amino acid sequence of any one of SEQ ID NOs: 19, 20, 21, 22, 23, 24, or 25.

12. The method of any one of claims 9-11, wherein the IgG protease is covalently or non- covalently conjugated to the N-terminus, or the C-terminus of the Fc polypeptide via a linker.

13. The method of claim 12, wherein the linker is a peptide linker.

14. The method of any one of claims 9-13, wherein the IgG protease comprises, from N- terminus to C-terminus: the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1303; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1290;the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1291; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1292; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1293; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1294; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1295; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1296; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1297; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1298; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1299; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1300; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1301; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1302; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1304; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1305; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1306;the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1307; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1308; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1309; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1310; the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23, a peptide linker, and the polypeptide having an amino acid sequence of SEQ ID NO: 1333; the polypeptide having an amino acid sequence of SEQ ID NO: 1290, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1291, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1292, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1293, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1294, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1295, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1296, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1297, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1298, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1299, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23;the polypeptide having an amino acid sequence of SEQ ID NO: 1300, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1301, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1302, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1303, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23 the polypeptide having an amino acid sequence of SEQ ID NO: 1304, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1305, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1306, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1307, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1308, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1309, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; the polypeptide having an amino acid sequence of SEQ ID NO: 1310, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23; or the polypeptide having an amino acid sequence of SEQ ID NO: 1333, a peptide linker, and the Fc polypeptide having an amino acid sequence of SEQ ID NO: 23.

15. The method of any one of claims 9-14, wherein the Fc polypeptide self-associates to form a dimer.

16. The method of claim 15, wherein the dimer is a homodimer or a heterodimer.

17. The method of any one of claims 9- 16, wherein the IgG protease comprises an amino acid sequence of any one of SEQ ID NOs: 1318, 1311, 1312, 1313, 1314, 1315, 1316, 1317, 1319, 1320, 1321, 1322, 1323, 1324, 1325, 1326, 1327, 1328, 1329, 1334, 1335, and 1336.

18. The method of any one of claims 1-17, wherein the therapeutic antibody comprises: a heavy chain 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 to an amino acid sequence selected from any one of SEQ ID NO: 1351, 1352, 1353, 1354,1355, 1356, 1357, 1358, 1359, 1360, 1361, 1362, 1363, 1364, 1365, 1366, 1367, 1368, 1369, 1370, 1371, 1372, 1373, 1374, 1375, 1376, 1377, 1378, 1379, 1380, 1381, 1382, 1383, 1384, 1385, 1386, 1387, 1388, 1389, 1391, 1392, 1393, and 1394, provided that the amino acid sequence comprises a mutation, or a set of mutations of:Y296Q;F296Q;P329K;Y296Q and P329K; orF296Q and P329K, wherein the mutation or set of mutations are in the Fc domain of the heavy chain, according to EU numbering; a heavy chain 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 to an amino acid sequence selected from any one of SEQ ID NO: 1352, 1353, 1354, 1355,1356, 1357, 1358, 1359, 1362, 1363, 1364, 1365, 1366, 1368, 1370, 1371, 1372, 1374, 1375, 1376, 1377, 1378, 1379, 1381, 1383, 1384, 1385, 1386, 1388, 1389, 1391, and 1392, provided that the amino acid sequence comprises a mutation, or a set of mutations of:Y296Q;P329K; orY296Q and P329K,wherein the mutation or set of mutations are in the Fc domain of the heavy chain, according to EU numbering; or a heavy chain 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 to an amino acid sequence selected from any one of SEQ ID NO: 1351, 1360, 1361, 1367, 1369, 1373, 1380, 1387, 1393, and 1394, provided that the amino acid sequence comprises a mutation, or a set of mutations of:F296Q;P329K; orF296Q and P329K, wherein the mutation or set of mutations are in the Fc domain of the heavy chain, according to EU numbering.

19. The method of any one of claims 1-18, wherein: the therapeutic antibody Rituxan (rituximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1353, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Ocrevus (ocrelizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1355, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Orencia (abatacept) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1359, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Stelara (ustekinumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1365, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Cosentyx (secukinumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1366, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Tremfya (guselkumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1372, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Skyrizi (risankizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1374, or 1375, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Skyrizi (risankizumab) comprises a set of heavy chains having amino acid sequences that are 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 to amino acid sequences of SEQ ID NOs: 1374 and 1375, provided that eachamino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Dupixent (dupilumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1380, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Actemra (tocilizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1384, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Enbrel (etanercept) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1389, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Humira (adalimumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1390, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Tysabri (natalizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1351, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Benlysta (belimumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1352, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Saphnelo (anifrolumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1362, or 1363, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Saphnelo (anifrolumab) comprises a set of heavy chains having amino acid sequences that are 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 to amino acid sequences of SEQ ID NOs: 1362 and 1363, provided that each amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Xolair (omalizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1364, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Taltz (ixekizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1367, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Bimzelx (bimekizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1368, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Nucala (mepolizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1381, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Fasenra (benralizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1383, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Prolia (denosumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1387, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Remicade (infliximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1388, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Simponi (golimumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1391, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Entyvio (vedolizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1392, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Briumvi (ublituximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1354, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Orthoclone Okt3 (Muromonab-CD3) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1356, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody MabCampath / Lemtrada (lemtuzumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1357, provided that the aminoacid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Alzumab (itolizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1358, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Veopoz (pozelimab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1360, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Soliris (eculizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1361, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Siliq (brodalumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1369, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Haris (canakinumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1370, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Arcalyst (rilonacept) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1371, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Omvoh (mirikizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1373, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Ilumya (tildrakizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1376, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Simulect (basiliximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1377, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Zenapax (daclizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1378, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Spevigo (spesolimab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1379, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Cinqair (reslizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1382, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Kevzara (sarilumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1385, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Sylvant (siltuximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1386, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Adbry (tralokinumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1393, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; or the therapeutic antibody Ebglyss (lebrikizumab) 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 to an amino acid sequence of SEQ ID NO: 1394, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering.

20. The method of any one of claims 1-19, wherein the IgG heavy chain Fc domain or the Fc domain is resistant to proteolytic cleavage.

21. The method of claim 1, wherein the (a) IgG protease and the (b) enzyme replacement therapy (ERT), or the therapeutic antibody are administered concurrently or separately.

22. The method of any one of claims 1-21, wherein the disease or disorder is selected from multiple sclerosis, Crohn’s disease, lupus, psoriasis, protein-losing enteropathy, paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, pericarditis, multi-system inflammatory syndrome, generalized postural psoriasis, Castleman’s disease, osteoporosis, autoimmune thyroid disease, Addison's disease, Anti-GBM glomerulonephritis, anti-neutrophil cytoplasmic antibody-associated vasculitides, ANCA associated vasculitis, granulomatous polyangiitis (Wegener granulomatosis), eosinophilic granulomatosis with polyangiitis (Churg- Strauss syndrome), microscopic polyangiitis, anti-NMDAR encephalitis, anti-phospholipid antibody syndrome (APS) and catastrophic APS, autoimmune bullous skin diseases, pemphigus, pemphigus foliaceus (PF), fogo selvage (FS), pemphigus vulgaris (PV), autoimmune hemolytic anemia (AIHA), autoimmune hepatitis (AIH), autoimmune neutropenia (AIN), bullous pemphigoid (BP), Celiac’s disease, chronic urticaria, complete congenital heart block (CCHB), diabetes type 1A (T1DM), epidermolysis bullosa acquisita (EBA), essential mixed cryoglobulinemia, Goodpasture’s syndrome, anti-glomerular basement membrane disease, Graves’ disease, Goitre, hyperthyroidism, infiltrative exophthalmos, infiltrative dermopathy, Guillain-Barre syndrome (GBS), acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), hemophilia, acquired FVII deficiency, idiopathicthrombocytopenic purpura (ITP), Lambert-Eaton myasthenic syndrome (LEMS), mixed connective tissue disease (MCTD), multiple myeloma, myasthenia gravis, myasthenic crisis, myocarditis, dilated cardiomyopathy (DCM), congestive cardiomyopathy, neuromyelitis optica (NMO), primary biliary cirrhosis (PBC), primary progressive multiple sclerosis (PPMS), relapsing-rheumatic multiple sclerosis, acute exacerbation of multiple sclerosis, rheumatic heart disease (RHD), rheumatoid arthritis (RA), serum-sickness, immune complex hypersensitivity (type III), Sjogren’s syndrome (SS), lupus nephritis, systemic lupus erythematosus (SLE), cutaneous lupus (CLE), transplant rejection, thrombotic thrombocytopenic purpura (TTP), idiopathic inflammatory myopathies, polymyositis, dermatomyositis, inclusion body myositis, uveitis, scleritis, ankylosing spondylitis, axial spondyloarthritis, reactive arthritis, psoriatic arthritis, IBD-associated arthritis, antiphospholipid syndrome, systemic sclerosis, giant cell arteritis, polymyalgia rheumatic, Takayasu’s arteritis, anti-neutrophil cytoplasmic antibody associated vasculitis, Henoch-Schonlein purpura, polyarteritis nodosa, Cogan’s syndrome, Buerger’s disease, Susan’s disease, immune complex vasculitis, primary angiitis of the central nervous system (CNS), Behcet’s disease, relapsing polychondritis, juvenile idiopathic arthritis, juvenile dermatomyositis, autoimmune brain disease, sarcoidosis, neurosarcoidosis, IgG4-related diseases, autoimmune complications of immune checkpoint inhibitors (IRAEs), adult onset Still’s disease, warm antibody hemolytic anemia (wAIHA), immune thrombocytopenia, immune thrombotic thrombocytopenia, thrombic thrombocytopenia, pernicious anemia, aplastic anemia, Evan’s syndrome, autoimmune neutropenia, acquired von Willibrand syndrome, recurring fetal loss, Rh mismatch, ulcerative colitis, autoimmune hepatitis, autoimmune pancreatitis, eosinophilic esophagitis / gastritis, primary sclerosing cholangitis, primary biliary sclerosis, glomerulonephritis, glomerular basement membrane disease, scleritis / episcleritis, uveitis, conjunctivitis, keratitis, type I diabetes mellitus, Hashimoto’s thyroiditis, polyglandular autoimmune endocrine syndromes, atopic dermatitis, dermatitis herpetiformis, pemphigus foliaceus, fogo selvagem, cutaneous lupus erythematosus, linear IgA disease, Lichen planus, transplantation, antibody-mediated rejection, alloantibody hypersensitization, xenoantibody mediated rejection, solid organ rejection, graft vs. host disease (GVHD), multiple sclerosis, neuromyelitis optica, amyotrophic lateral sclerosis, Parkinson’s disease, autoimmune encephalitis, CNS vasculitis, chronic idiopathic demyletinating polyneuropathy, transverse myelitis, optic neuritis, anti-myelin oligodendrocyte glycoprotein (MOG) disease, chronicmeningitis, rheumatic heart disease, infectious disease, vaccination, antibody dependent enhancement, antibody to therapeutic biologic agents (cytokines, monoclonal antibodies, enzymes, coagulation factors), allergic asthma, eosinophilic pneumonia, nonspecific interstitial pneumonia, rheumatoid arthritis-associated interstitial lung disease (RA-ILD), sarcoidosis, hypersensitive pneumonitis, allergic bronchopulmonary mycosis, chronic rhinosinusitis with nasal polyps, Pompe disease, Fabry disease, or any combination thereof.

23. A method of treating a disease or a disorder in a subject in need thereof, the method comprising administering to the subject:(a) an IgG protease comprising an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 55-1019; and(b) an enzyme replacement therapy (ERT), or a therapeutic antibody, wherein: the ERT is a recombinant enzyme linked to an Fc domain comprising a mutation, or a set of mutations of Y296Q, F296Q, and / or P329K according to EU numbering, and the therapeutic antibody comprises an IgG heavy chain Fc domain comprising a mutation, or a set of mutations of Y296Q, F296Q, and / or P329K in the Fc domain of the heavy chain, according to EU numbering.

24. The method of claim 23, wherein the therapeutic antibody is selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Dupixent (dupilumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Tysabri (natalizumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Taltz (ixekizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Prolia (denosumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Haris (canakinumab), Arcalyst (rilonacept), Omvoh (mirikizumab), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spevigo (spesolimab), Cinqair (reslizumab), Kevzara (sarilumab), Sylvant(siltuximab), Adbry (tralokinumab), Ebglyss (lebrikizumab), any combination thereof, and any variant thereof.

25. The method of claim 23, wherein the IgG protease is less immunogenic than a wild-type IdeS.

26. The method of any one of claims 23-25, wherein the IgG protease comprises the amino acid sequence of any one of SEQ ID NOs: 55-1019.

27. The method of any one of claims 23-26, wherein the IgG protease is covalently or non- covalently conjugated to an Fc polypeptide.

28. The method of claim 27, wherein the Fc polypeptide comprises an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 19, 20, 21, 22, 23, 24, or 25.

29. The method of claim 28, wherein the Fc polypeptide comprises an amino acid sequence of any one of SEQ ID NOs: 19, 20, 21, 22, 23, 24, or 25.

30. The method of any one of claims 27-29, wherein the IgG protease is covalently or non- covalently conjugated to the N-terminus, or the C-terminus of the Fc polypeptide via a linker.

31. The method of claim 30, wherein the linker is a peptide linker.

32. The method of any one of claims 27-31, wherein the Fc polypeptide self-associates, or associates with another Fc polypeptide, to form a dimer.

33. The method of claim 32, wherein the dimer is a homodimer or a heterodimer.

34. The method of any one of claims 27-33, wherein the IgG protease comprises an amino acid sequence of any one of SEQ ID NOs: 1023-1289.

35. The method of any one of claims 23-34, wherein the therapeutic antibody comprises: a heavy chain 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 to an amino acid sequence selected from any one of SEQ ID NO: 1351, 1352, 1353, 1354,1355, 1356, 1357, 1358, 1359, 1360, 1361, 1362, 1363, 1364, 1365, 1366, 1367, 1368,1369, 1370, 1371, 1372, 1373, 1374, 1375, 1376, 1377, 1378, 1379, 1380, 1381, 1382,1383, 1384, 1385, 1386, 1387, 1388, 1389, 1391, 1392, 1393, and 1394, provided that the amino acid sequence comprises a mutation, or a set of mutations of:Y296Q;F296Q;P329K;Y296Q and P329K; orF296Q and P329K, wherein the mutation or set of mutations are in the Fc domain of the heavy chain, according to EU numbering; a heavy chain 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 to an amino acid sequence selected from any one of SEQ ID NO: 1352, 1353, 1354, 1355,1356, 1357, 1358, 1359, 1362, 1363, 1364, 1365, 1366, 1368, 1370, 1371, 1372, 1374, 1375, 1376, 1377, 1378, 1379, 1381, 1383, 1384, 1385, 1386, 1388, 1389, 1391, and 1392, provided that the amino acid sequence comprises a mutation, or a set of mutations of:Y296Q;P329K; orY296Q and P329K,wherein the mutation or set of mutations are in the Fc domain of the heavy chain, according to EU numbering; or a heavy chain 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 to an amino acid sequence selected from any one of SEQ ID NO: 1351, 1360, 1361, 1367, 1369, 1373, 1380, 1387, 1393, and 1394, provided that the amino acid sequence comprises a mutation, or a set of mutations of:F296Q;P329K; orF296Q and P329K, wherein the mutation or set of mutations are in the Fc domain of the heavy chain, according to EU numbering.

36. The method of any one of claims 23-35, wherein: the therapeutic antibody Rituxan (rituximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1353, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Ocrevus (ocrelizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1355, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Orencia (abatacept) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1359, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Stelara (ustekinumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1365, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Cosentyx (secukinumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1366, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Tremfya (guselkumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1372, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Skyrizi (risankizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1374, or 1375, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Skyrizi (risankizumab) comprises a set of heavy chains having amino acid sequences that are 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 to amino acid sequences of SEQ ID NOs: 1374 and 1375, provided that eachamino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Dupixent (dupilumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1380, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Actemra (tocilizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1384, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Enbrel (etanercept) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1389, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Humira (adalimumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1390, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Tysabri (natalizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1351, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Benlysta (belimumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1352, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Saphnelo (anifrolumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1362, or 1363, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Saphnelo (anifrolumab) comprises a set of heavy chains having amino acid sequences that are 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 to amino acid sequences of SEQ ID NOs: 1362 and 1363, provided that each amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Xolair (omalizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1364, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Taltz (ixekizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1367, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Bimzelx (bimekizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1368, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Nucala (mepolizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1381, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Fasenra (benralizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1383, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Prolia (denosumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1387, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Remicade (infliximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1388, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Simponi (golimumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1391, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Entyvio (vedolizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1392, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Briumvi (ublituximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1354, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Orthoclone Okt3 (Muromonab-CD3) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1356, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody MabCampath / Lemtrada (lemtuzumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1357, provided that the aminoacid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Alzumab (itolizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1358, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Veopoz (pozelimab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1360, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Soliris (eculizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1361, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Siliq (brodalumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1369, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Haris (canakinumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1370, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Arcalyst (rilonacept) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1371, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Omvoh (mirikizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1373, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Ilumya (tildrakizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1376, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Simulect (basiliximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1377, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Zenapax (daclizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1378, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Spevigo (spesolimab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1379, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Cinqair (reslizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1382, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Kevzara (sarilumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1385, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Sylvant (siltuximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1386, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Adbry (tralokinumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1393, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; or the therapeutic antibody Ebglyss (lebrikizumab) 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 to an amino acid sequence of SEQ ID NO: 1394, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering.

37. The method of any one of claims 23-36, wherein the Fc domain of the heavy chain is resistant to proteolytic cleavage.

38. The method of claim 23, wherein the (a) IgG protease and the (b) enzyme replacement therapy (ERT), or the therapeutic antibody are administered concurrently or separately.

39. The method of any one of claims 23-38, wherein the disease or disorder is selected from multiple sclerosis, Crohn’s disease, lupus, psoriasis, protein-losing enteropathy, paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, pericarditis, multi-system inflammatory syndrome, generalized postural psoriasis, Castleman’s disease, osteoporosis, autoimmune thyroid disease, Addison's disease, Anti-GBM glomerulonephritis, anti-neutrophil cytoplasmic antibody-associated vasculitides, ANCA associated vasculitis, granulomatous polyangiitis (Wegener granulomatosis), eosinophilic granulomatosis with polyangiitis (Churg- Strauss syndrome), microscopic polyangiitis, anti-NMDAR encephalitis, anti-phospholipid antibody syndrome (APS) and catastrophic APS, autoimmune bullous skin diseases, pemphigus, pemphigus foliaceus (PF), fogo selvage (FS), pemphigus vulgaris (PV), autoimmune hemolytic anemia (AIHA), autoimmune hepatitis (AIH), autoimmune neutropenia (AIN), bullous pemphigoid (BP), Celiac’s disease, chronic urticaria, complete congenital heart block (CCHB), diabetes type 1A (T1DM), epidermolysis bullosa acquisita (EBA), essential mixed cryoglobulinemia, Goodpasture’s syndrome, anti-glomerular basement membrane disease, Graves’ disease, Goitre, hyperthyroidism, infiltrative exophthalmos, infiltrative dermopathy, Guillain-Barre syndrome (GBS), acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), hemophilia, acquired FVII deficiency, idiopathicthrombocytopenic purpura (ITP), Lambert-Eaton myasthenic syndrome (LEMS), mixed connective tissue disease (MCTD), multiple myeloma, myasthenia gravis, myasthenic crisis, myocarditis, dilated cardiomyopathy (DCM), congestive cardiomyopathy, neuromyelitis optica (NMO), primary biliary cirrhosis (PBC), primary progressive multiple sclerosis (PPMS), relapsing-rheumatic multiple sclerosis, acute exacerbation of multiple sclerosis, rheumatic heart disease (RHD), rheumatoid arthritis (RA), serum-sickness, immune complex hypersensitivity (type III), Sjogren’s syndrome (SS), lupus nephritis, systemic lupus erythematosus (SLE), cutaneous lupus (CLE), transplant rejection, thrombotic thrombocytopenic purpura (TTP), idiopathic inflammatory myopathies, polymyositis, dermatomyositis, inclusion body myositis, uveitis, scleritis, ankylosing spondylitis, axial spondyloarthritis, reactive arthritis, psoriatic arthritis, IBD-associated arthritis, antiphospholipid syndrome, systemic sclerosis, giant cell arteritis, polymyalgia rheumatic, Takayasu’s arteritis, anti-neutrophil cytoplasmic antibody associated vasculitis, Henoch-Schonlein purpura, polyarteritis nodosa, Cogan’s syndrome, Buerger’s disease, Susan’s disease, immune complex vasculitis, primary angiitis of the central nervous system (CNS), Behcet’s disease, relapsing polychondritis, juvenile idiopathic arthritis, juvenile dermatomyositis, autoimmune brain disease, sarcoidosis, neurosarcoidosis, IgG4-related diseases, autoimmune complications of immune checkpoint inhibitors (IRAEs), adult onset Still’s disease, warm antibody hemolytic anemia (wAIHA), immune thrombocytopenia, immune thrombotic thrombocytopenia, thrombic thrombocytopenia, pernicious anemia, aplastic anemia, Evan’s syndrome, autoimmune neutropenia, acquired von Willibrand syndrome, recurring fetal loss, Rh mismatch, ulcerative colitis, autoimmune hepatitis, autoimmune pancreatitis, eosinophilic esophagitis / gastritis, primary sclerosing cholangitis, primary biliary sclerosis, glomerulonephritis, glomerular basement membrane disease, scleritis / episcleritis, uveitis, conjunctivitis, keratitis, type I diabetes mellitus, Hashimoto’s thyroiditis, polyglandular autoimmune endocrine syndromes, atopic dermatitis, dermatitis herpetiformis, pemphigus foliaceus, fogo selvagem, cutaneous lupus erythematosus, linear IgA disease, Lichen planus, transplantation, antibody-mediated rejection, alloantibody hypersensitization, xenoantibody mediated rejection, solid organ rejection, graft vs. host disease (GVHD), multiple sclerosis, neuromyelitis optica, amyotrophic lateral sclerosis, Parkinson’s disease, autoimmune encephalitis, CNS vasculitis, chronic idiopathic demyletinating polyneuropathy, transverse myelitis, optic neuritis, anti-myelin oligodendrocyte glycoprotein (MOG) disease, chronicmeningitis, rheumatic heart disease, infectious disease, vaccination, antibody dependent enhancement, antibody to therapeutic biologic agents (cytokines, monoclonal antibodies, enzymes, coagulation factors), allergic asthma, eosinophilic pneumonia, nonspecific interstitial pneumonia, rheumatoid arthritis-associated interstitial lung disease (RA-ILD), sarcoidosis, hypersensitive pneumonitis, allergic bronchopulmonary mycosis, chronic rhinosinusitis with nasal polyps, Pompe disease, Fabry disease, or any combination thereof.

40. A method of reducing immunoglobulins in a subject in need thereof; treating a transplant subject in need thereof; improving a gene-therapy in subject in need thereof; treating a subject having, or at risk, or elevated risk, for having, an IgG mediated disease or disorder; or cleaving B cell receptor in a subject in need thereof, the method comprising administering to the subject:(a) an IgG protease and comprising an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 55-1019; and(b) an enzyme replacement therapy (ERT), or a therapeutic antibody, wherein: the ERT is a recombinant enzyme linked to an Fc domain comprising a mutation, or a set of mutations of Y296Q, F296Q, and / or P329K according to EU numbering, and the therapeutic antibody comprises an IgG heavy chain Fc domain comprising a mutation, or a set of mutations of Y296Q, F296Q, and / or P329K in the Fc domain of the heavy chain, according to EU numbering.

41. The method of claim 40, wherein the therapeutic antibody is selected from Rituxan (rituximab), Ocrevus (ocrelizumab), Orencia (abatacept), Stelara (ustekinumab), Cosentyx (secukinumab), Tremfya (guselkumab), Skyrizi (risankizumab), Dupixent (dupilumab), Actemra (tocilizumab), Enbrel (etanercept), Humira (adalimumab), Tysabri (natalizumab), Benlysta (belimumab), Saphnelo (anifrolumab), Xolair (omalizumab), Taltz (ixekizumab), Bimzelx (bimekizumab), Nucala (mepolizumab), Fasenra (benralizumab), Prolia (denosumab), Remicade (infliximab), Simponi (golimumab), Entyvio (vedolizumab), Briumvi (ublituximab), Orthoclone Okt3 (Muromonab-CD3), MabCampath / Lemtrada (lemtuzumab), Alzumab (itolizumab), Veopoz (pozelimab), Soliris (eculizumab), Siliq (brodalumab), Haris (canakinumab), Arcalyst(rilonacept), Omvoh (mirikizumab), Ilumya (tildrakizumab), Simulect (basiliximab), Zenapax (daclizumab), Spcvigo (spcsolimab), Cinqair (rcslizumab), Kcvzara (sarilumab), Sylvant (siltuximab), Adbry (tralokinumab), Ebglyss (lebrikizumab), any combination thereof, and any variant thereof.

42. The method of claim 40, wherein the IgG protease is less immunogenic than a wild-type IdeS.

43. The method of any one of claims 40-42, wherein the IgG protease comprises the amino acid sequence of any one of SEQ ID NOs: 55-1019.

44. The method of any one of claims 40-43, wherein the IgG protease is covalently or non- covalently conjugated to an Fc polypeptide.

45. The method of claim 44, wherein the Fc polypeptide comprises an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 19, 20, 21, 22, 23, 24, or 25.

46. The method of claim 45, wherein the Fc polypeptide comprises an amino acid sequence of any one of SEQ ID NOs: 19, 20, 21, 22, 23, 24, or 25.

47. The method of any one of claims 44-46, wherein the IgG protease is covalently or non- covalently conjugated to the N-terminus, or the C-terminus of the Fc polypeptide via a linker.

48. The method of claim 47, wherein the linker is a peptide linker.

49. The method of any one of claims 44-48, wherein the Fc polypeptide self-associates, or associates with another Fc polypeptide, to form a dimer.

50. The method of claim 49, wherein the dimer is a homodimer or a heterodimer.

51. The method of any one of claims 44-50, wherein the IgG protease comprises an amino acid sequence of any one of SEQ ID NOs: 1023-1289.

52. The method of any one of claims 40-51, wherein the therapeutic antibody comprises: a heavy chain 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 to an amino acid sequence selected from any one of SEQ ID NO: 1351, 1352, 1353, 1354,1355, 1356, 1357, 1358, 1359, 1360, 1361, 1362, 1363, 1364, 1365, 1366, 1367, 1368, 1369, 1370, 1371, 1372, 1373, 1374, 1375, 1376, 1377, 1378, 1379, 1380, 1381, 1382, 1383, 1384, 1385, 1386, 1387, 1388, 1389, 1391, 1392, 1393, and 1394, provided that the amino acid sequence comprises a mutation, or a set of mutations of:Y296Q;F296Q;P329K;Y296Q and P329K; orF296Q and P329K, wherein the mutation or set of mutations are in the Fc domain of the heavy chain, according to EU numbering; a heavy chain 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 to an amino acid sequence selected from any one of SEQ ID NO: 1352, 1353, 1354, 1355,1356, 1357, 1358, 1359, 1362, 1363, 1364, 1365, 1366, 1368, 1370, 1371, 1372, 1374, 1375, 1376, 1377, 1378, 1379, 1381, 1383, 1384, 1385, 1386, 1388, 1389, 1391, and 1392, provided that the amino acid sequence comprises a mutation, or a set of mutations of:Y296Q;P329K; orY296Q and P329K,wherein the mutation or set of mutations are in the Fc domain of the heavy chain, according to EU numbering; or a heavy chain 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 to an amino acid sequence selected from any one of SEQ ID NO: 1351, 1360, 1361, 1367, 1369, 1373, 1380, 1387, 1393, and 1394, provided that the amino acid sequence comprises a mutation, or a set of mutations of:F296Q;P329K; orF296Q and P329K, wherein the mutation or set of mutations are in the Fc domain of the heavy chain, according to EU numbering.

53. The method of any one of claims 40-52, wherein: the therapeutic antibody Rituxan (rituximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1353, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Ocrevus (ocrelizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1355, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Orencia (abatacept) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1359, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Stelara (ustekinumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1365, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Cosentyx (secukinumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1366, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Tremfya (guselkumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1372, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Skyrizi (risankizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1374, or 1375, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Skyrizi (risankizumab) comprises a set of heavy chains having amino acid sequences that are 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 to amino acid sequences of SEQ ID NOs: 1374 and 1375, provided that eachamino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Dupixent (dupilumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1380, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Actemra (tocilizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1384, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Enbrel (etanercept) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1389, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Humira (adalimumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1390, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Tysabri (natalizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1351, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Benlysta (belimumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1352, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Saphnelo (anifrolumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1362, or 1363, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Saphnelo (anifrolumab) comprises a set of heavy chains having amino acid sequences that are 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 to amino acid sequences of SEQ ID NOs: 1362 and 1363, provided that each amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Xolair (omalizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1364, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Taltz (ixekizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1367, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Bimzelx (bimekizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1368, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Nucala (mepolizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1381, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Fasenra (benralizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1383, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Prolia (denosumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1387, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Remicade (infliximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1388, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Simponi (golimumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1391, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Entyvio (vedolizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1392, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Briumvi (ublituximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1354, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Orthoclone Okt3 (Muromonab-CD3) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1356, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody MabCampath / Lemtrada (lemtuzumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1357, provided that the aminoacid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Alzumab (itolizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1358, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Veopoz (pozelimab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1360, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Soliris (eculizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1361, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Siliq (brodalumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1369, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Haris (canakinumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1370, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Arcalyst (rilonacept) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1371, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Omvoh (mirikizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1373, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Ilumya (tildrakizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1376, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Simulect (basiliximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1377, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Zenapax (daclizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1378, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Spevigo (spesolimab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1379, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Cinqair (reslizumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1382, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Kevzara (sarilumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1385, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Sylvant (siltuximab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1386, provided that the amino acid sequence comprises a mutation, or a set of mutations of: Y296Q; P329K; or Y296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; the therapeutic antibody Adbry (tralokinumab) comprises a heavy chain having an amino acid sequence that is 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 to an amino acid sequence of SEQ ID NO: 1393, provided that the amino acid sequencecomprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering; or the therapeutic antibody Ebglyss (lebrikizumab) 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 to an amino acid sequence of SEQ ID NO: 1394, provided that the amino acid sequence comprises a mutation, or a set of mutations of: F296Q; P329K; or F296Q and P329K in the Fc domain of the heavy chain, according to EU numbering.

54. The method of any one of claims 40-53, wherein the Fc domain of the heavy chain is resistant to proteolytic cleavage.

55. The method of claim 40, wherein the (a) IgG protease and the (b) enzyme replacement therapy (ERT), or the therapeutic antibody are administered concurrently or separately.

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