Method for delivering FC fusion molecule

Abstract

The present invention provides, among other things, a method of treating a disease or disorder comprising administering an Fc fusion molecule that binds neonatal Fc receptor (FcRn) at a therapeutically effective dosing regimen, wherein the Fc fusion molecule comprises a modified Fc region, a linker and an albumin or an albumin binding domain.

Description

Attorney Docket No. VRD-024WO1METHOD FOR DELIVERING FC FUSION MOLECULECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to, and the benefit of, U.S. Provisional Application No. 63 / 719,079, filed November 11, 2024, and U.S. Provisional No. 63 / 721,527, filed November 17, 2024, the disclosure of each of which is hereby incorporated by reference in its entirety.BACKGROUND

[0002] Immunoglobulin gamma (IgG) antibodies play a key role in the pathology of many disorders, such as autoimmune diseases, inflammatory diseases, and ocular disorders. IgGs generally have a longer half-life than other plasma proteins, in part, due to the binding of the Fc region of IgG to the Fc receptor, FcRn. Although FcRn was originally characterized as a neonatal transport receptor for maternal IgG, it also functions in adults to protect IgG from degradation. FcRn binds to pinocytosed IgG and protects the IgG from transport to degradative lysosomes by recycling it back to the extracellular compartment where it is released from FcRn and can resume its biological function.

[0003] Human serum albumin (HSA), produced by the liver, is the most abundant plasma protein with high solubility, high stability, and a long circulatory half-life. HSA has several functions, including acting as a drug transport protein and carrier for many metabolites and fatty acids. HSA can also be used to improve the half-life of therapeutic proteins.

[0004] Therapeutics targeting FcRn generally function to inhibit recycling of IgGs by binding to domains responsible for recycling these molecules. As a result, IgG based FcRn antagonists may have a shorter half-life than other therapeutics due to a reduction in the recycling mechanism. As such, there is a need for improved FcRn antagonists with longer half-life.SUMMARY OF THE INVENTION

[0005] The present invention provides, among other things, a method for treating a disease or disorder comprising administering an Fc fusion molecule that binds to neonatal Fc receptor (FcRn) at a therapeutically effective dosing regimen. The method described herein allows, among other things, (1) durable IgG suppression while maintaining safety profile of an FcAttorney Docket No. VRD-024WO1 fragment; (2) less frequent administration of the Fc fusion molecule; and / or (3) less frequent intravenous or subcutaneous injection, including self-administered injections.

[0006] In one aspect, the present invention provides, among other things, a method of treating an immunoglobulin G (IgG)-mediated disease or disorder comprising subcutaneously administering an Fc fusion molecule that binds neonatal Fc receptor (FcRn) at a dose of between 300 mg to 3000 mg, wherein the Fc fusion molecule comprises from N-terminus to C-terminus or C-terminus to N-terminus: (a) an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; (b) a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and (c) a sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0007] In one aspect, the present invention provides, among other things, a method for reducing an IgG level in a subject comprising subcutaneously administering an Fc fusion molecule that binds neonatal Fc receptor (FcRn) at a dose of between 300 mg to 3000 mg, wherein the Fc fusion molecule comprises from N-terminus to C-terminus or C-terminus to N-terminus: (a) an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; (b) a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and (c) a sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0008] In some embodiments, the Fc fusion molecule comprises from N-terminus to C- terminus: (a) an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; (b) a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and (c) a sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101). In some embodiments, the Fc fusion molecule comprises from C-terminus to N-terminus: (a) an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; (b) a linker comprising one or more repeating units ofAttorney Docket No. VRD-024WO1GGGGS (SEQ ID NO: 181); and (c) a sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0009] In some embodiments, the Fc fusion molecule is administered at a dose of 300 mg to 2400 mg, 300 mg to 1200 mg, 300 mg to 600 mg, 600 mg to 3000 mg, 600 mg to 2400 mg, 600 mg to 1200 mg, 1200 mg to 3000 mg, 1200 mg to 2400 mg, or 2400 mg to 3000 mg. In some embodiments, the Fc fusion molecule is administered at a dose of 300 mg to 2400 mg. In some embodiments, the Fc fusion molecule is administered at a dose of 300 mg to 1200 mg. In some embodiments, the Fc fusion molecule is administered at a dose of 300 mg to 600 mg. In some embodiments, the Fc fusion molecule is administered at a dose of 600 mg to 3000 mg. In some embodiments, the Fc fusion molecule is administered at a dose of 600 mg to 2400 mg. In some embodiments, the Fc fusion molecule is administered at a dose of 600 mg to 1200 mg. In some embodiments, the Fc fusion molecule is administered at a dose of 1200 mg to 3000 mg. In some embodiments, the Fc fusion molecule is administered at a dose of 1200 mg to 2400 mg. In some embodiments, the Fc fusion molecule is administered at a dose of 2400 mg to 3000 mg.

[0010] In some embodiments, the dose is 300 mg, 600 mg, 1200 mg, 2400 mg, or 3000 mg. In some embodiments, the dose is 300 mg. In some embodiments, the dose is 600 mg. In some embodiments, the dose is 1200 mg. In some embodiments, the dose is 2400 mg. In some embodiments, the dose is 3000 mg.[OH] In some embodiments, the Fc fusion molecule is administered with a syringe pump delivery system. In some embodiments, the syringe pump delivery system is an on-body device. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 0.5 mL / min to 2.0 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 0.5 mL / min to 1.5 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 0.5 mL / min to 1.0 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 0.5 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 0.6 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 0.7 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 0.8 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 0.9 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate ofAttorney Docket No. VRD-024WO11.0 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 1.1 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 1.2 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 1.3 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 1.4 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 1.5 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 1.6 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 1.7 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 1.8 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 1.9 mL / min. In some embodiments, the Fc fusion molecule is administered at an infusion rate of 2.0 mL / min. In some embodiments, the Fc fusion molecule dose is administered in 2 min to 30 min. In some embodiments, the Fc fusion molecule dose is administered in 2.5 min to 25 min. In some embodiments, the Fc fusion molecule dose is administered in 5 min to 30 min. In some embodiments, the Fc fusion molecule dose is administered in 5 min to 25 min. In some embodiments, the Fc fusion molecule dose is administered in 10 min to 30 min. In some embodiments, the Fc fusion molecule dose is administered in 10 min to 25 min. In some embodiments, the Fc fusion molecule dose is administered in 5 min to 20 min. In some embodiments, the Fc fusion molecule dose is administered in 2 min to 20 min. In some embodiments, the Fc fusion molecule dose is administered in 10 min to 20 min. In some embodiments, the Fc fusion molecule dose is administered in 10 min to 15 min. In some embodiments, the Fc fusion molecule dose is administered in 5 min to 15 min. In some embodiments, the Fc fusion molecule dose is administered in 15 min to 30 min. In some embodiments, the Fc fusion molecule dose is administered in 15 min to 25 min.

[0012] In some embodiments, the Fc fusion molecule is administered no more frequently than once every week. In some embodiments, the Fc fusion molecule is administered no more frequently than once every two weeks. In some embodiments, the Fc fusion molecule is administered no more frequently than once every three weeks. In some embodiments, the Fc fusion molecule is administered no more frequently than once every four weeks. In some embodiments, the Fc fusion molecule is administered no more frequently than once every five weeks. In some embodiments, the Fc fusion molecule is administered no more frequently than once every six weeks. In some embodiments, the Fc fusion molecule is administered noAttorney Docket No. VRD-024WO1 more frequently than once every seven weeks. In some embodiments, the Fc fusion molecule is administered no more frequently than once every eight weeks.

[0013] In some embodiments, the Fc fusion molecule is administered once every week. In some embodiments, the Fc fusion molecule is administered once every two weeks. In some embodiments, the Fc fusion molecule is administered once every three weeks. In some embodiments, the Fc fusion molecule is administered once every four weeks. In some embodiments, the Fc fusion molecule is administered once every five weeks. In some embodiments, the Fc fusion molecule is administered once every six weeks. In some embodiments, the Fc fusion molecule is administered once every seven weeks. In some embodiments, the Fc fusion molecule is administered once every eight weeks.

[0014] In one aspect, the present invention provides, among other things, a method of treating an immunoglobulin G (IgG)-mediated disease or disorder comprising intravenously administering an Fc fusion molecule that binds neonatal Fc receptor (FcRn) at a dose of between 1 mg / kg to 50 mg / kg, wherein the Fc fusion molecule comprises from N-terminus to C-terminus or C-terminus to N-terminus: (a) an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; (b) a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and (c) a sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0015] In one aspect, the present invention provides, among other things, a method for reducing an IgG level in a subject comprising intravenously administering an Fc fusion molecule that binds neonatal Fc receptor (FcRn) at a dose of between 1 mg / kg to 50 mg / kg, wherein the Fc fusion molecule comprises from N-terminus to C-terminus or C-terminus to N-terminus: (a) an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; (b) a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and (c) a sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0016] In some embodiments, the Fc fusion molecule is administered at a dose of 1 mg / kg to 6 mg / kg, 3 mg / kg to 7 mg / kg, 4 mg / kg to 10 mg / kg, 5 mg / kg to 11 mg / kg, 6 mg / kg to 12Attorney Docket No. VRD-024WO1 mg / kg, 7 mg / kg to 13 mg / kg, 8 mg / kg to 14 mg / kg, 9 mg / kg to 15 mg / kg, 10 mg / kg to 16 mg / kg, 11 mg / kg to 17 mg / kg, 12 mg / kg to 18 mg / kg, 13 mg / kg to 19 mg / kg, 14 mg / kg to 20 mg / kg, 10 mg / kg to 20 mg / kg, 15 mg / kg to 20 mg / kg, 20 mg / kg to 30 mg / kg, 25 mg / kg to 30 mg / kg, 25 mg / kg to 35 mg / kg, 30 mg / kg to 35 mg / kg, 30 mg / kg to 40 mg / kg, 35 mg / kg to 40 mg / kg, 40 mg / kg to 50 mg / kg, or 45 mg / kg to 50 mg / kg.

[0017] In some embodiments, the Fc fusion molecule is administered at a dose of 1 mg / kg to 6 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 3 mg / kg to 7 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 4 mg / kg to 10 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 5 mg / kg to 11 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 6 mg / kg to 12 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 7 mg / kg to 13 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 8 mg / kg to 14 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 9 mg / kg to 15 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 10 mg / kg to 16 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 11 mg / kg to 17 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 12 mg / kg to 18 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 13 mg / kg to 19 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 14 mg / kg to 20 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 10 mg / kg to 20 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 15 mg / kg to 20 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 20 mg / kg to 30 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 25 mg / kg to 30 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 25 mg / kg to 35 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 30 mg / kg to 35 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 30 mg / kg to 40 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 35 mg / kg to 40 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 40 mg / kg to 50 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 45 mg / kg to 50 mg / kg.

[0018] In some embodiments, the Fc fusion molecule is administered at a dose of 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19Attorney Docket No. VRD-024WO1 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, 24 mg / kg, 25 mg / kg, 26 mg / kg, 27 mg / kg, 28 mg / kg, 29 mg / kg, 30 mg / kg, 31 mg / kg, 32 mg / kg, 33 mg / kg, 34 mg / kg, 35 mg / kg, 36 mg / kg, 37 mg / kg, 38 mg / kg, 39 mg / kg, 40 mg / kg, 41 mg / kg, 42 mg / kg, 43 mg / kg, 44 mg / kg, 45 mg / kg, 46 mg / kg, 47 mg / kg, 48 mg / kg, 49 mg / kg, or 50 mg / kg.

[0019] In some embodiments, the Fc fusion molecule is administered at a dose of 1 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 2 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 3 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 4 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 5 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 6 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 7 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 8 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 9 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 10 mg / kg.

[0020] In some embodiments, the Fc fusion molecule is administered at a dose of 11 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 12 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 13 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 14 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 15 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 16 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 17 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 18 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 19 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 20 mg / kg.

[0021] In some embodiments, the Fc fusion molecule is administered at a dose of 21 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 22 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 23 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 24 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 25 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 26 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 27 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 28 mg / kg. In someAttorney Docket No. VRD-024WO1 embodiments, the Fc fusion molecule is administered at a dose of 29 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 30 mg / kg.

[0022] In some embodiments, the Fc fusion molecule is administered at a dose of 31 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 32 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 33 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 34 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 35 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 36 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 37 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 38 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 39 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 40 mg / kg.

[0023] In some embodiments, the Fc fusion molecule is administered at a dose of 41 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 42 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 43 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 44 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 45 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 46 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 47 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 48 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 49 mg / kg. In some embodiments, the Fc fusion molecule is administered at a dose of 50 mg / kg.

[0024] In some embodiments, the Fc fusion molecule dose is administered at an infusion rate of 4.2 mL / min.

[0025] In some embodiments, the Fc fusion molecule is administered in a single dose.

[0026] In some embodiments, administering the Fc fusion molecule reduces the IgG level to less than 90%, to less than 85%, to less than 80%, to less than 75%, to less than 70%, to less than 65%, to less than 60%, to less than 55%, to less than 50% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level to less than 90% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level to less than 85% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments,Attorney Docket No. VRD-024WO1 administering the Fc fusion molecule reduces the IgG level to less than 80% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level to less than 75% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level to less than 70% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level to less than 65% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level to less than 60% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level to less than 55% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level to less than 50% as compared to an IgG level prior to the administration of the Fc fusion molecule.

[0027] In some embodiments, administering the Fc fusion molecule reduces the IgG level for more than 10 days, more than 15 days, more than 20 days, more than 25 days, or more than 30 days as compared to an IgG level prior to administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level for more than 10 days as compared to an IgG level prior to administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level for more than 15 days as compared to an IgG level prior to administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level for more than 20 days as compared to an IgG level prior to administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level for more than 25 days as compared to an IgG level prior to administration of the Fc fusion molecule. In some embodiments, administering the Fc fusion molecule reduces the IgG level for more than 30 days as compared to an IgG level prior to administration of the Fc fusion molecule.

[0028] In some embodiments, the Fc region comprises a lysine at the C-terminus. In some embodiments, the Fc region does not comprise a lysine at the C-terminus.

[0029] In some embodiments, the Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the FcAttorney Docket No. VRD-024WO1 region comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 15, 18- 19, 34, or 37. In some embodiments, the Fc region comprises an amino acid sequence identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37.

[0030] In some embodiments, the Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 15.

[0031] In some embodiments, the Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an aminoAttorney Docket No. VRD-024WO1 acid sequence at least 99% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 18.

[0032] In some embodiments, the Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 19.

[0033] In some embodiments, the Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 34.

[0034] In some embodiments, the Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 37. In someAttorney Docket No. VRD-024WO1 embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 37.

[0035] In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 85% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 90% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 95% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 96% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 97% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 98% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 99% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence identical to SEQ ID NO: 55.

[0036] In some embodiments, the Fc fusion molecule forms a homodimer. In some embodiments, the Fc fusion molecule forms a heterodimer.

[0037] In some embodiments, the Fc fusion molecule comprises a first polypeptide comprising, from N-terminus to C-terminus a first Fc region, the linker, and the sdAb; and a second polypeptide comprising a second Fc region. In some embodiments, the Fc fusion molecule comprises a first polypeptide comprising, from C-terminus to N-terminus a first Fc region, the linker, and the sdAb; and a second polypeptide comprising a second Fc region.

[0038] In some embodiments, the first Fc region and the second Fc region comprise the same amino acid substitutions. In some embodiments, the first Fc region and the second Fc region comprise different amino acid substitutions.

[0039] In some embodiments, the Fc fusion molecule is co-administered with hyaluronidase. In some embodiments, the Fc fusion molecule is not co-administered with hyaluronidase.

[0040] In one aspect, the present invention provides, among other things, a method of treating an IgG-mediated disease or disorder comprising subcutaneously administering aAttorney Docket No. VRD-024WO1 molecule that binds neonatal Fc receptor (FcRn) at a dose of between 300 mg to 3000 mg, wherein the molecule comprises a first polypeptide comprising from N-terminus to C- terminus or C-terminus to N-terminus: a first Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and a sdAb comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index.

[0041] In one aspect, the present invention provides, among other things, a method of treating an IgG-mediated disease or disorder comprising subcutaneously administering a molecule that binds neonatal Fc receptor (FcRn) at a dose of between 300 mg to 3000 mg, wherein the molecule comprises a first polypeptide comprising from N-terminus to C- terminus or C-terminus to N-terminus: a first Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and a sdAb comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index.

[0042] In one aspect, the present invention provides, among other things, a method for reducing an IgG level in a subject comprising subcutaneously administering a molecule that binds neonatal Fc receptor (FcRn) at a dose of between 300 mg to 3000 mg, wherein the molecule comprises a first polypeptide comprising from N-terminus to C-terminus or C- terminus to N-terminus: a first Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and a sdAb comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3Attorney Docket No. VRD-024WO1 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index.

[0043] In some embodiments, the first polypeptide comprises from N-terminus to C- terminus: a first Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and a sdAb comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101). In some embodiments, the first polypeptide comprises from C-terminus to N-terminus: a first Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and a sdAb comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0044] In some embodiments, the molecule is administered at a dose of 300 mg to 2400 mg, 300 mg to 1200 mg, 300 mg to 600 mg, 600 mg to 3000 mg, 600 mg to 2400 mg, 600 mg to 1200 mg, 1200 mg to 3000 mg, 1200 mg to 2400 mg, or 2400 mg to 3000 mg. In some embodiments, the molecule is administered at a dose of 300 mg to 2400 mg. In some embodiments, the molecule is administered at a dose of 300 mg to 1200 mg. In some embodiments, the molecule is administered at a dose of 300 mg to 600 mg. In some embodiments, the molecule is administered at a dose of 600 mg to 3000 mg. In some embodiments, the molecule is administered at a dose of 600 mg to 2400 mg. In some embodiments, the molecule is administered at a dose of 600 mg to 1200 mg. In some embodiments, the molecule is administered at a dose of 1200 mg to 3000 mg. In some embodiments, the molecule is administered at a dose of 1200 mg to 2400 mg. In some embodiments, the molecule is administered at a dose of 2400 mg to 3000 mg.

[0045] In some embodiments, the dose is 300 mg, 600 mg, 1200 mg, 2400 mg, or 3000 mg. In some embodiments, the dose is 300 mg. In some embodiments, the dose is 600 mg. In some embodiments, the dose is 1200 mg. In some embodiments, the dose is 2400 mg. In some embodiments, the dose is 3000 mg.Attorney Docket No. VRD-024WO1

[0046] In some embodiments, the molecule is administered with a syringe pump delivery system. In some embodiments, the syringe pump delivery system is an on-body device. In some embodiments, the molecule is administered at an infusion rate of 0.5 mL / min to 2.0 mL / min. In some embodiments, the molecule is administered at an infusion rate of 0.5 mL / min to 1.5 mL / min. In some embodiments, the molecule is administered at an infusion rate of 0.5 mL / min to 1.0 mL / min. In some embodiments, the molecule is administered at an infusion rate of 0.5 mL / min. In some embodiments, the molecule is administered at an infusion rate of 0.6 mL / min. In some embodiments, the molecule is administered at an infusion rate of 0.7 mL / min. In some embodiments, the molecule is administered at an infusion rate of 0.8 mL / min. In some embodiments, the molecule is administered at an infusion rate of 0.9 mL / min. In some embodiments, the molecule is administered at an infusion rate of 1.0 mL / min. In some embodiments, the molecule is administered at an infusion rate of 1.1 mL / min. In some embodiments, the molecule is administered at an infusion rate of 1.2 mL / min. In some embodiments, the molecule is administered at an infusion rate of 1.3 mL / min. In some embodiments, the molecule is administered at an infusion rate of 1.4 mL / min. In some embodiments, the molecule is administered at an infusion rate of 1.5 mL / min. In some embodiments, the molecule is administered at an infusion rate of 1.6 mL / min. In some embodiments, the molecule is administered at an infusion rate of 1.7 mL / min. In some embodiments, the molecule is administered at an infusion rate of 1.8 mL / min. In some embodiments, the molecule is administered at an infusion rate of 1.9 mL / min. In some embodiments, the molecule is administered at an infusion rate of 2.0 mL / min. In some embodiments, the molecule dose is administered in 2 min to 30 min. In some embodiments, the molecule dose is administered in 2.5 min to 25 min. In some embodiments, the molecule dose is administered in 5 min to 30 min. In some embodiments, the molecule dose is administered in 5 min to 25 min. In some embodiments, the molecule dose is administered in 10 min to 30 min. In some embodiments, the molecule dose is administered in 10 min to 25 min. In some embodiments, the molecule dose is administered in 5 min to 20 min. In some embodiments, the molecule dose is administered in 2 min to 20 min. In some embodiments, the molecule dose is administered in 10 min to 20 min. In some embodiments, the molecule dose is administered in 10 min to 15 min. In some embodiments, the molecule dose is administered in 5 min to 15 min. In some embodiments, the molecule dose is administered in 15 min to 30 min. In some embodiments, the molecule dose is administered in 15 min to 25 min.Attorney Docket No. VRD-024WO1

[0047] In some embodiments, the molecule is administered no more frequently than once every week. In some embodiments, the molecule is administered no more frequently than once every two weeks. In some embodiments, the molecule is administered no more frequently than once every three weeks. In some embodiments, the molecule is administered no more frequently than once every four weeks. In some embodiments, the molecule is administered no more frequently than once every five weeks. In some embodiments, the molecule is administered no more frequently than once every six weeks. In some embodiments, the molecule is administered no more frequently than once every seven weeks. In some embodiments, the molecule is administered no more frequently than once every eight weeks.

[0048] In some embodiments, the molecule is administered once every week. In some embodiments, the molecule is administered once every two weeks. In some embodiments, the molecule is administered once every three weeks. In some embodiments, the molecule is administered once every four weeks. In some embodiments, the molecule is administered once every five weeks. In some embodiments, the molecule is administered once every six weeks. In some embodiments, the molecule is administered once every seven weeks. In some embodiments, the molecule is administered once every eight weeks.

[0049] In one aspect, the present invention provides, among other things, a method of treating an IgG-mediated disease or disorder comprising intravenously administering a molecule that binds neonatal Fc receptor (FcRn) at a dose of between 1 mg / kg to 50 mg / kg, wherein the molecule comprises a first polypeptide comprising from N-terminus to C- terminus or C-terminus to N-terminus: a first Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and a sdAb comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index.

[0050] In one aspect, the present invention provides, among other things, a method for reducing an IgG level in a subject comprising intravenously administering a molecule that binds neonatal Fc receptor (FcRn) at a dose of between 1 mg / kg to 50 mg / kg, wherein theAttorney Docket No. VRD-024WO1 molecule comprises a first polypeptide comprising from N-terminus to C-terminus or C- terminus to N-terminus: a first Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and a sdAb comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index.

[0051] In some embodiments, the molecule is administered at a dose of 1 mg / kg to 6 mg / kg, 3 mg / kg to 7 mg / kg, 4 mg / kg to 10 mg / kg, 5 mg / kg to 11 mg / kg, 6 mg / kg to 12 mg / kg, 7 mg / kg to 13 mg / kg, 8 mg / kg to 14 mg / kg, 9 mg / kg to 15 mg / kg, 10 mg / kg to 16 mg / kg, 11 mg / kg to 17 mg / kg, 12 mg / kg to 18 mg / kg, 13 mg / kg to 19 mg / kg, 14 mg / kg to 20 mg / kg, 10 mg / kg to 20 mg / kg, 15 mg / kg to 20 mg / kg, 20 mg / kg to 30 mg / kg, 25 mg / kg to 30 mg / kg, 25 mg / kg to 35 mg / kg, 30 mg / kg to 35 mg / kg, 30 mg / kg to 40 mg / kg, 35 mg / kg to 40 mg / kg, 40 mg / kg to 50 mg / kg, or 45 mg / kg to 50 mg / kg.

[0052] In some embodiments, the molecule is administered at a dose of 1 mg / kg to 6 mg / kg. In some embodiments, the molecule is administered at a dose of 3 mg / kg to 7 mg / kg. In some embodiments, the molecule is administered at a dose of 4 mg / kg to 10 mg / kg. In some embodiments, the molecule is administered at a dose of 5 mg / kg to 11 mg / kg. In some embodiments, the molecule is administered at a dose of 6 mg / kg to 12 mg / kg. In some embodiments, the molecule is administered at a dose of 7 mg / kg to 13 mg / kg. In some embodiments, the molecule is administered at a dose of 8 mg / kg to 14 mg / kg. In some embodiments, the molecule is administered at a dose of 9 mg / kg to 15 mg / kg. In some embodiments, the molecule is administered at a dose of 10 mg / kg to 16 mg / kg. In some embodiments, the molecule is administered at a dose of 11 mg / kg to 17 mg / kg. In some embodiments, the molecule is administered at a dose of 12 mg / kg to 18 mg / kg. In some embodiments, the molecule is administered at a dose of 13 mg / kg to 19 mg / kg. In some embodiments, the molecule is administered at a dose of 14 mg / kg to 20 mg / kg. In some embodiments, the molecule is administered at a dose of 10 mg / kg to 20 mg / kg. In some embodiments, the molecule is administered at a dose of 15 mg / kg to 20 mg / kg. In some embodiments, the molecule is administered at a dose of 20 mg / kg to 30 mg / kg. In someAttorney Docket No. VRD-024WO1 embodiments, the molecule is administered at a dose of 25 mg / kg to 30 mg / kg. In some embodiments, the molecule is administered at a dose of 25 mg / kg to 35 mg / kg. In some embodiments, the molecule is administered at a dose of 30 mg / kg to 35 mg / kg. In some embodiments, the molecule is administered at a dose of 30 mg / kg to 40 mg / kg. In some embodiments, the molecule is administered at a dose of 35 mg / kg to 40 mg / kg. In some embodiments, the molecule is administered at a dose of 40 mg / kg to 50 mg / kg. In some embodiments, the molecule is administered at a dose of 45 mg / kg to 50 mg / kg.

[0053] In some embodiments, the molecule is administered at a dose of 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, 24 mg / kg, 25 mg / kg, 26 mg / kg, 27 mg / kg, 28 mg / kg, 29 mg / kg, 30 mg / kg, 31 mg / kg, 32 mg / kg, 33 mg / kg, 34 mg / kg, 35 mg / kg, 36 mg / kg, 37 mg / kg, 38 mg / kg, 39 mg / kg, 40 mg / kg, 41 mg / kg, 42 mg / kg, 43 mg / kg, 44 mg / kg, 45 mg / kg, 46 mg / kg, 47 mg / kg, 48 mg / kg, 49 mg / kg, or 50 mg / kg.

[0054] In some embodiments, the molecule is administered at a dose of 1 mg / kg. In some embodiments, the molecule is administered at a dose of 2 mg / kg. In some embodiments, the molecule is administered at a dose of 3 mg / kg. In some embodiments, the molecule is administered at a dose of 4 mg / kg. In some embodiments, the molecule is administered at a dose of 5 mg / kg. In some embodiments, the molecule is administered at a dose of 6 mg / kg. In some embodiments, the molecule is administered at a dose of 7 mg / kg. In some embodiments, the molecule is administered at a dose of 8 mg / kg. In some embodiments, the molecule is administered at a dose of 9 mg / kg. In some embodiments, the molecule is administered at a dose of 10 mg / kg.

[0055] In some embodiments, the molecule is administered at a dose of 11 mg / kg. In some embodiments, the molecule is administered at a dose of 12 mg / kg. In some embodiments, the molecule is administered at a dose of 13 mg / kg. In some embodiments, the molecule is administered at a dose of 14 mg / kg. In some embodiments, the molecule is administered at a dose of 15 mg / kg. In some embodiments, the molecule is administered at a dose of 16 mg / kg. In some embodiments, the molecule is administered at a dose of 17 mg / kg. In some embodiments, the molecule is administered at a dose of 18 mg / kg. In some embodiments, the molecule is administered at a dose of 19 mg / kg. In some embodiments, the molecule is administered at a dose of 20 mg / kg.Attorney Docket No. VRD-024WO1

[0056] In some embodiments, the molecule is administered at a dose of 21 mg / kg. In some embodiments, the molecule is administered at a dose of 22 mg / kg. In some embodiments, the molecule is administered at a dose of 23 mg / kg. In some embodiments, the molecule is administered at a dose of 24 mg / kg. In some embodiments, the molecule is administered at a dose of 25 mg / kg. In some embodiments, the molecule is administered at a dose of 26 mg / kg. In some embodiments, the molecule is administered at a dose of 27 mg / kg. In some embodiments, the molecule is administered at a dose of 28 mg / kg. In some embodiments, the molecule is administered at a dose of 29 mg / kg. In some embodiments, the molecule is administered at a dose of 30 mg / kg.

[0057] In some embodiments, the molecule is administered at a dose of 31 mg / kg. In some embodiments, the molecule is administered at a dose of 32 mg / kg. In some embodiments, the molecule is administered at a dose of 33 mg / kg. In some embodiments, the molecule is administered at a dose of 34 mg / kg. In some embodiments, the molecule is administered at a dose of 35 mg / kg. In some embodiments, the molecule is administered at a dose of 36 mg / kg. In some embodiments, the molecule is administered at a dose of 37 mg / kg. In some embodiments, the molecule is administered at a dose of 38 mg / kg. In some embodiments, the molecule is administered at a dose of 39 mg / kg. In some embodiments, the molecule is administered at a dose of 40 mg / kg.

[0058] In some embodiments, the molecule is administered at a dose of 41 mg / kg. In some embodiments, the molecule is administered at a dose of 42 mg / kg. In some embodiments, the molecule is administered at a dose of 43 mg / kg. In some embodiments, the molecule is administered at a dose of 44 mg / kg. In some embodiments, the molecule is administered at a dose of 45 mg / kg. In some embodiments, the molecule is administered at a dose of 46 mg / kg. In some embodiments, the molecule is administered at a dose of 47 mg / kg. In some embodiments, the molecule is administered at a dose of 48 mg / kg. In some embodiments, the molecule is administered at a dose of 49 mg / kg. In some embodiments, the molecule is administered at a dose of 50 mg / kg.

[0059] In some embodiments, the molecule dose is administered at an infusion rate of 4.2 mL / min.

[0060] In some embodiments, the molecule is administered in a single dose.

[0061] In some embodiments, administering the molecule reduces the IgG level to less than 90%, to less than 85%, to less than 80%, to less than 75%, to less than 70%, to less than 65%, to less than 60%, to less than 55%, to less than 50% as compared to an IgG level priorAttorney Docket No. VRD-024WO1 to the administration of the molecule. In some embodiments, administering the molecule reduces the IgG level to less than 90% as compared to an IgG level prior to the administration of the molecule. In some embodiments, administering the molecule reduces the IgG level to less than 85% as compared to an IgG level prior to the administration of the molecule. In some embodiments, administering the molecule reduces the IgG level to less than 80% as compared to an IgG level prior to the administration of the molecule. In some embodiments, administering the molecule reduces the IgG level to less than 75% as compared to an IgG level prior to the administration of the molecule. In some embodiments, administering the molecule reduces the IgG level to less than 70% as compared to an IgG level prior to the administration of the molecule. In some embodiments, administering the molecule reduces the IgG level to less than 65% as compared to an IgG level prior to the administration of the molecule. In some embodiments, administering the molecule reduces the IgG level to less than 60% as compared to an IgG level prior to the administration of the molecule. In some embodiments, administering the molecule reduces the IgG level to less than 55% as compared to an IgG level prior to the administration of the molecule. In some embodiments, administering the molecule reduces the IgG level to less than 50% as compared to an IgG level prior to the administration of the molecule.

[0062] In some embodiments, administering the molecule reduces the IgG level for more than 10 days, more than 15 days, more than 20 days, more than 25 days, or more than 30 days as compared to an IgG level prior to administration of the molecule. In some embodiments, administering the molecule reduces the IgG level for more than 10 days as compared to an IgG level prior to administration of the molecule. In some embodiments, administering the molecule reduces the IgG level for more than 15 days as compared to an IgG level prior to administration of the molecule. In some embodiments, administering the molecule reduces the IgG level for more than 20 days as compared to an IgG level prior to administration of the molecule. In some embodiments, administering the molecule reduces the IgG level for more than 25 days as compared to an IgG level prior to administration of the molecule. In some embodiments, administering the molecule reduces the IgG level for more than 30 days as compared to an IgG level prior to administration of the molecule.

[0063] In some embodiments, the first Fc region and / or the second Fc region comprise a lysine at the C-terminus. In some embodiments, the first Fc region and / or the second Fc region do not comprise a lysine at the C-terminus. In some embodiments, the first Fc region or the second Fc region comprises a lysine at the C-terminus. In some embodiments, the firstAttorney Docket No. VRD-024WO1Fc region or the second Fc region does not comprise a lysine at the C-terminus. In some embodiments, the first Fc region and the second Fc region comprise a lysine at the C- terminus. In some embodiments, the first Fc region and the second Fc region do not comprise a lysine at the C-terminus.

[0064] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence identical to SEQ ID NO: 1.

[0065] In some embodiments, the first Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 15, 18- 19, 34, or 37; and the second Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37; and the second Fc region comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 15, 18- 19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37; and the second Fc region comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 15, 18- 19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37; and the second Fc region comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 15, 18- 19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37; and the second Fc region comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 15, 18- 19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence atAttorney Docket No. VRD-024WO1 least 97% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37; and the second Fc region comprises an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 15, 18- 19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37; and the second Fc region comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 15, 18- 19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37; and the second Fc region comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 15, 18- 19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37; and the second Fc region comprises an amino acid sequence identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37.

[0066] In some embodiments, the first Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 15, 18- 19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the first Fc region comprises an amino acid sequence identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37.

[0067] In some embodiments, the first Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15. In some embodiments, the first Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 15. In some embodiments, the first Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 15. In some embodiments, the first Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 15. In some embodiments, the first Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 15. InAttorney Docket No. VRD-024WO1 some embodiments, the first Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 15. In some embodiments, the first Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 15. In some embodiments, the first Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 15. In some embodiments, the first Fc region comprises an amino acid sequence identical to SEQ ID NO: 15.

[0068] In some embodiments, the first Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 18. In some embodiments, the first Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 18. In some embodiments, the first Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 18. In some embodiments, the first Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 18. In some embodiments, the first Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 18. In some embodiments, the first Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 18. In some embodiments, the first Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 18. In some embodiments, the first Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 18. In some embodiments, the first Fc region comprises an amino acid sequence identical to SEQ ID NO:18.

[0069] In some embodiments, the first Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence identical to SEQ ID NO:19.Attorney Docket No. VRD-024WO1

[0070] In some embodiments, the first Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 34. In some embodiments, the first Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 34. In some embodiments, the first Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 34. In some embodiments, the first Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 34. In some embodiments, the first Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 34. In some embodiments, the first Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 34. In some embodiments, the first Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 34. In some embodiments, the first Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 34. In some embodiments, the first Fc region comprises an amino acid sequence identical to SEQ ID NO: 34.

[0071] In some embodiments, the first Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence identical to SEQ ID NO: 37.

[0072] In some embodiments, the second Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 15, 18- 19, 34, or 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 15, 18-Attorney Docket No. VRD-024WO119, 34, or 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 15, 18- 19, 34, or 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37. In some embodiments, the second Fc region comprises an amino acid sequence identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37.

[0073] In some embodiments, the second Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15. In some embodiments, the second Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 15. In some embodiments, the second Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 15. In some embodiments, the second Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 15. In some embodiments, the second Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 15. In some embodiments, the second Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 15. In some embodiments, the second Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 15. In some embodiments, the second Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 15. In some embodiments, the second Fc region comprises an amino acid sequence identical to SEQ ID NO: 15.

[0074] In some embodiments, the second Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 18. In some embodiments, the second Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 18. In some embodiments, the second Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 18. In some embodiments, the second Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 18. In some embodiments, the second Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 18. In some embodiments, the second Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 18. In some embodiments, the second Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 18. In some embodiments, the second Fc region comprises an amino acid sequence at least 99% identicalAttorney Docket No. VRD-024WO1 to SEQ ID NO: 18. In some embodiments, the second Fc region comprises an amino acid sequence identical to SEQ ID NO: 18.

[0075] In some embodiments, the second Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 19. In some embodiments, the second Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 19. In some embodiments, the second Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 19. In some embodiments, the second Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 19. In some embodiments, the second Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 19. In some embodiments, the second Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 19. In some embodiments, the second Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 19. In some embodiments, the second Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 19. In some embodiments, the second Fc region comprises an amino acid sequence identical to SEQ ID NO: 19.

[0076] In some embodiments, the second Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 34. In some embodiments, the second Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 34. In some embodiments, the second Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 34. In some embodiments, the second Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 34. In some embodiments, the second Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 34. In some embodiments, the second Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 34. In some embodiments, the second Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 34. In some embodiments, the second Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 34. In some embodiments, the second Fc region comprises an amino acid sequence identical to SEQ ID NO: 34.

[0077] In some embodiments, the second Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 37. In some embodiments, the second FcAttorney Docket No. VRD-024WO1 region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 37. In some embodiments, the second Fc region comprises an amino acid sequence identical to SEQ ID NO: 37.

[0078] In some embodiments, the first Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 18; and the second Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 18; and the second Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 18; and the second Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 18; and the second Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 18; and the second Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 18; and the second Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 18; and the second Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 18; and the second Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 19. In some embodiments, the first Fc region comprises an amino acid sequence identical to SEQ ID NO: 18; and the second Fc region comprises an amino acid sequence identical to SEQ ID NO: 19.

[0079] In some embodiments, the first Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 34; and the secondAttorney Docket No. VRD-024WO1Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 34; and the second Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 34; and the second Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 34; and the second Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 34; and the second Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 34; and the second Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 34; and the second Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 34; and the second Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 37. In some embodiments, the first Fc region comprises an amino acid sequence identical to SEQ ID NO: 34; and the second Fc region comprises an amino acid sequence identical to SEQ ID NO: 37.

[0080] In some embodiments, the linker comprises one unit of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 2 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 3 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 4 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 5 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 6 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 7 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 8 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 9 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 10 repeating units of GGGGS (SEQ ID NO: 181).Attorney Docket No. VRD-024WO1

[0081] In some embodiments, the linker comprises 2 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 3 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 4 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 5 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 6 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 7 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 8 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 9 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 10 repeating units of GGGGS (SEQ ID NO: 181).

[0082] In some embodiments, the first Fc region further comprises amino acid substitutions T366S, L368A, and Y407V, and the second Fc region further comprises amino acid substitution T366W. In some embodiments, the second Fc region further comprises amino acid substitutions T366S, L368A, and Y407V, and the first Fc region further comprises amino acid substitution T366W. In some embodiments, the first Fc region further comprises amino acid substitutions Y349C, T366S, L368A, and Y407V, and the second Fc region further comprises amino acid substitutions S354C and T366W. In some embodiments, the second Fc region further comprises amino acid substitutions Y349C, T366S, L368A, and Y407V, and the first Fc region further comprises amino acid substitutions S354C and T366W.

[0083] In some embodiments, the first polypeptide comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 19. In some embodiments, the first polypeptide comprises an amino acid sequence at least 85% identical to SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence at least 85% identical to SEQ ID NO: 19. In some embodiments, the first polypeptide comprises an amino acid sequence at least 90% identical to SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence at least 90% identical to SEQ ID NO: 19. In some embodiments, the first polypeptide comprises an amino acid sequence at least 95% identical to SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence at least 95% identical to SEQ ID NO: 19. In some embodiments, the first polypeptide comprises an amino acid sequence at least 96% identical to SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence at leastAttorney Docket No. VRD-024WO196% identical to SEQ ID NO: 19. In some embodiments, the first polypeptide comprises an amino acid sequence at least 97% identical to SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence at least 97% identical to SEQ ID NO: 19. In some embodiments, the first polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NO: 19. In some embodiments, the first polypeptide comprises an amino acid sequence at least 99% identical to SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence at least 99% identical to SEQ ID NO: 19. In some embodiments, the first polypeptide comprises an amino acid sequence identical to SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence identical to SEQ ID NO: 19.

[0084] In some embodiments, the molecule is co-administered with hyaluronidase. In some embodiments, the molecule is not co-administered with hyaluronidase.

[0085] In some embodiments, the disease or disorder is an autoimmune disorder. In some embodiments, the disease or disorder is an inflammatory disorder. In some embodiments, the disease or disorder is an ocular disorder.

[0086] In some embodiments, the disease or disorder is generalized myasthenia gravis (gMG), Grave's disease, chronic inflammatory demyelinating polyneuropathy, myositis, autoimmune encephalitis, myelin oligodendrocyte glycoprotein antibody disorders (MOG- antibody disorder), membranous nephropathy, lupus nephritis, thyroid eye disease, warm autoimmune hemolytic anemia, hemolytic disease of the fetus and newborn, idiopathic inflammatory myopathy, idiopathic thrombocytopenic purpura, primary Sjogren’s Syndrome, systemic lupus erythematosus, rheumatoid arthritis, bullous pemphigoid, pemphigus foliaceus, pemphigus vulgaris, or cutaneous lupus erythematosus, antibody mediated rejection, systemic sclerosis, lupus neuropathy, or ocular myasthenia gravis.

[0087] In some embodiments, the disease or disorder is generalized myasthenia gravis (gMG). In some embodiments, the disease or disorder is Grave's disease. In some embodiments, the disease or disorder is chronic inflammatory demyelinating polyneuropathy. In some embodiments, the disease or disorder is myositis. In some embodiments, the disease or disorder is autoimmune encephalitis. In some embodiments, the disease or disorder is myelin oligodendrocyte glycoprotein antibody disorder (MOG-antibody disorder). In some embodiments, the disease or disorder is membranous nephropathy. In some embodiments, the disease or disorder is lupus nephritis. In some embodiments, the disease or disorder is thyroidAttorney Docket No. VRD-024WO1 eye disease. In some embodiments, the disease or disorder is warm autoimmune hemolytic anemia. In some embodiments, the disease or disorder is hemolytic disease of the fetus and newborn. In some embodiments, the disease or disorder is an idiopathic inflammatory myopathy. In some embodiments, the disease or disorder is idiopathic thrombocytopenic purpura. In some embodiments, the disease or disorder is primary Sjogren’s Syndrome. In some embodiments, the disease or disorder is systemic lupus erythematosus. In some embodiments, the disease or disorder is rheumatoid arthritis. In some embodiments, the disease or disorder is bullous pemphigoid. In some embodiments, the disease or disorder is pemphigus foliaceus. In some embodiments, the disease or disorder is pemphigus vulgaris. In some embodiments, the disease or disorder is cutaneous lupus erythematosus. In some embodiments, the disease or disorder is antibody mediated rejection. In some embodiments, the disease or disorder is systemic sclerosis. In some embodiments, the disease or disorder is lupus neuropathy. In some embodiments, the disease or disorder is ocular myasthenia gravis.

[0088] In some embodiments, the disease or disorder is associated with elevated levels of an IgG.

[0089] In one aspect, the present invention provides, among other things, a method of treating a disease or disorder, wherein the method comprises administering an Fc fusion molecule that binds neonatal Fc receptor (FcRn) at a therapeutically effective dosing regimen.

[0090] In one aspect, the present invention provides a method for reducing an IgG level in a subject, wherein the method comprises administering an Fc fusion molecule that binds to FcRn at a therapeutically effective dosing regimen sufficient to reduce the IgG level in the subject for more than 15 days. In some embodiments, the IgG level is reduced to less than 80%, to less than 60%, to less than 50% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reduced to less than 80% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reduced to less than 75% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reduced to less than 70% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reduced to less than 65% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reduced to less than 60% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reducedAttorney Docket No. VRD-024WO1 to less than 55% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reduced to less than 50% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reduced to less than 45% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reduced to less than 40% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reduced to less than 35% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reduced to less than 30% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reduced to less than 25% as compared to an IgG level prior to the administration of the Fc fusion molecule. In some embodiments, the IgG level is reduced to less than 20% as compared to an IgG level prior to the administration of the Fc fusion molecule.

[0091] In some embodiments, the IgG level is reduced for more than 20 days, more than 25 days, or more than 30 days. In some embodiments, the IgG level is reduced for more than 10 days. In some embodiments, the IgG level is reduced for more than 15 days. In some embodiments, the IgG level is reduced for more than 20 days. In some embodiments, the IgG level is reduced for more than 25 days. In some embodiments, the IgG level is reduced for more than 30 days. In some embodiments, the IgG level is reduced for more than 35 days. In some embodiments, the IgG level is reduced for more than 40 days. In some embodiments, the IgG level is reduced for more than 45 days. In some embodiments, the IgG level is reduced for more than 50 days.

[0092] In some embodiments, the Fc fusion molecule comprises, from N-terminus to C- terminus, an Fc region, a linker, and an albumin binding domain. In some embodiments, the Fc fusion molecule comprises, from C-terminus to N-terminus, an Fc region, a linker, and an albumin binding domain. In some embodiments, the Fc fusion molecule comprises, from N- terminus to C-terminus, an Fc region, a linker, and an albumin. In some embodiments, the Fc fusion molecule comprises, from C-terminus to N-terminus, an Fc region, a linker, and an albumin.

[0093] In some embodiments, the albumin binding domain is linked to the N-terminus of the Fc region via the linker. In some embodiments, the albumin binding domain is linked to the C-terminus of the Fc region via the linker. In some embodiments, the albumin binding domain is linked to an internal region in the Fc region via the linker. In some embodiments,Attorney Docket No. VRD-024WO1 the albumin is linked to the N-terminus of the Fc region via the linker. In some embodiments, the albumin is linked to the C-terminus of the Fc region via the linker. In some embodiments, the albumin is linked to an internal region in the Fc region via the linker.

[0094] In some embodiments, the Fc fusion molecule comprises, from N-terminus to C- terminus, an Fc region comprising amino acid substitutions (i) N434Y and (ii) H433R or H433K as compared to an amino acid sequence set forth in SEQ ID NO: 12; a linker; and an albumin. In some embodiments, the Fc fusion molecule comprises, from N-terminus to C- terminus, an Fc region comprising amino acid substitutions (i) N434Y and (ii) H433R or H433K as compared to an amino acid sequence set forth in SEQ ID NO: 12; a linker; and an albumin binding domain. In some embodiments, the Fc fusion molecule comprises, from C- terminus to N-terminus, an Fc region comprising amino acid substitutions (i) N434Y and (ii) H433R or H433K as compared to an amino acid sequence set forth in SEQ ID NO: 12; a linker; and an albumin. In some embodiments, the Fc fusion molecule comprises, from C- terminus to N-terminus, an Fc region comprising amino acid substitutions (i) N434Y and (ii) H433R or H433K as compared to an amino acid sequence set forth in SEQ ID NO: 12; a linker; and an albumin binding domain. In some embodiments, the Fc region comprises amino acid substitutions of N434Y and H433R. In some embodiments, the Fc region comprises amino acid substitutions of N434Y and H433K.

[0095] In some embodiments, the Fc fusion molecule comprises, from N-terminus to C- terminus, an Fc region comprising amino acid substitutions M428L and N434F as compared to an amino acid sequence set forth in SEQ ID NO: 12; a linker; and an albumin. In some embodiments, the Fc fusion molecule comprises, from N-terminus to C-terminus, an Fc region comprising amino acid substitutions M428L and N434F as compared to an amino acid sequence set forth in SEQ ID NO: 12; a linker; and an albumin binding domain. In some embodiments, the Fc fusion molecule comprises, from C-terminus to N-terminus, an Fc region comprising amino acid substitutions M428L and N434F as compared to an amino acid sequence set forth in SEQ ID NO: 12; a linker; and an albumin. In some embodiments, the Fc fusion molecule comprises, from C-terminus to N-terminus, an Fc region comprising amino acid substitutions M428L and N434F as compared to an amino acid sequence set forth in SEQ ID NO: 12; a linker; and an albumin binding domain. In some embodiments, the Fc region further comprises an amino acid substitution of H433K.

[0096] In some embodiments, the linker is a chemical linker. In some embodiments, the linker is a peptide linker.Attorney Docket No. VRD-024WO1

[0097] In some embodiments, the linker comprises glycine and serine. In some embodiments, the linker comprises one or more repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises one unit of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 2 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 3 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 4 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 5 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 6 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 7 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 8 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 9 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises at least 10 repeating units of GGGGS (SEQ ID NO: 181).

[0098] In some embodiments, the linker comprises 2 repeating units of GGGGS. In some embodiments, the linker comprises 3 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 4 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 5 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 6 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 7 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 8 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 9 repeating units of GGGGS (SEQ ID NO: 181). In some embodiments, the linker comprises 10 repeating units of GGGGS (SEQ ID NO: 181).

[0099] In some embodiments, the Fc fusion molecule comprises an albumin. In some embodiments, the Fc fusion molecule comprises an albumin binding domain. In some embodiments, the albumin binding domain comprises an antibody or an antibody fragment. In some embodiments, the antibody or antibody fragment comprises a chimeric antibody, a humanized antibody, a single domain antibody (sdAb), a Fab, a Fab’, a (Fab’)2, an Fv, a single chain antibody (e.g., scFv), a minibody, a diabody, a VH, a VL, or an antibody mimetic.

[0100] In some embodiments, the albumin binding domain comprises a chimeric antibody. In some embodiments, the albumin binding domain comprises a humanized antibody. In some embodiments, the albumin binding domain comprises a single domain antibody (sdAb). In some embodiments, the albumin binding domain comprises a Fab. In some embodiments,Attorney Docket No. VRD-024WO1 the albumin binding domain comprises a Fab’. In some embodiments, the albumin binding domain comprises a (Fab’)2. In some embodiments, the albumin binding domain comprises a Fv. In some embodiments, the albumin binding domain comprises a single chain antibody (e.g., scFv). In some embodiments, the albumin binding domain comprises a minibody. In some embodiments, the albumin binding domain comprises an a diabody. In some embodiments, the albumin binding domain comprises a VH. In some embodiments, the albumin binding domain comprises a VL. In some embodiments, the albumin binding domain comprises an antibody mimetic.

[0101] In some embodiments, the albumin binding domain comprises an anti-HSA sdAb. In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0102] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AIDSGGADTRYAESVKG (SEQ ID NO: 96), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more thanAttorney Docket No. VRD-024WO12 amino acid residues from GRSASR (SEQ ID NO: 102). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AIDSGGADTRYAESVKG (SEQ ID NO: 96), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GRSASR (SEQ ID NO: 102). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AIDSGGADTRYAESVKG (SEQ ID NO: 96), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GRSASR (SEQ ID NO: 102). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGADTRYAESVKG (SEQ ID NO: 96), and a CDR3 comprising an amino acid sequence of GRSASR (SEQ ID NO: 102).

[0103] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AISSDGSGTIYADSVKG (SEQ ID NO: 97), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AISSDGSGTIYADSVKG (SEQ ID NO: 97), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AISSDGSGTIYADSVKG (SEQ ID NO: 97), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence of AISSDGSGTIYADSVKG (SEQ ID NO: 97), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).Attorney Docket No. VRD-024WO1

[0104] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AISSDASGTIYADSVKG (SEQ ID NO: 98), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AISSDASGTIYADSVKG (SEQ ID NO: 98), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AISSDASGTIYADSVKG (SEQ ID NO: 98), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence of AISSDASGTIYADSVKG (SEQ ID NO: 98), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0105] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AISSDSSGTIYADSVKG (SEQ ID NO: 99), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AISSDSSGTIYADSVKG (SEQ ID NO: 99), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AISSDSSGTIYADSVKG (SEQ IDAttorney Docket No. VRD-024WO1NO: 99), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence of AISSDSSGTIYADSVKG (SEQ ID NO: 99), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0106] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AIDSGGADTRYAETVKG (SEQ ID NO: 100), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GRSTSR (SEQ ID NO: 104). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AIDSGGADTRYAETVKG (SEQ ID NO: 100), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GRSTSR (SEQ ID NO: 104). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AIDSGGADTRYAETVKG (SEQ ID NO: 100), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GRSTSR (SEQ ID NO: 104). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGADTRYAETVKG (SEQ ID NO: 100), and a CDR3 comprising an amino acid sequence of GRSTSR (SEQ ID NO: 104).

[0107] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from SAGMS (SEQ ID NO: 93), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from SAGMS (SEQ ID NO: 93), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AIDSGGTDTRYAESIKG (SEQ IDAttorney Docket No. VRD-024WO1NO: 95), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from SAGMS (SEQ ID NO: 93), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of SAGMS (SEQ ID NO: 93), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0108] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from SFGAS (SEQ ID NO: 94), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from SFGAS (SEQ ID NO: 94), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from SFGAS (SEQ ID NO: 94), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of SFGAS (SEQ ID NO: 94), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0109] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AIDSGGTDTR (SEQ IDAttorney Docket No. VRD-024WO1NO: 110), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence of AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 comprising an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0110] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGRSASR (SEQ ID NO: 116). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGRSASR (SEQ ID NO: 116). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGRSASR (SEQ ID NO: 116). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence ofAttorney Docket No. VRD-024WO1AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence of TIGRSASR (SEQ ID NO: 116).

[0111] In some embodiments, the sdAb comprises AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AISSDGSGTI (SEQ ID NO: 112), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AISSDGSGTI (SEQ ID NO: 112), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AISSDGSGTI (SEQ ID NO: 112), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 comprising an amino acid sequence of AISSDGSGTI (SEQ ID NO: 112), and a CDR3 comprising an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0112] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AISSDASGTI (SEQ ID NO: 113), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AISSDASGTI (SEQ ID NO: 113), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AASGFTFGQFGMS (SEQ ID NO: 106),Attorney Docket No. VRD-024WO1 a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AISSDASGTI (SEQ ID NO: 113), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 comprising an amino acid sequence of AISSDASGTI (SEQ ID NO: 113), and a CDR3 comprising an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0113] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AISSDSSGTI (SEQ ID NO: 114), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AISSDSSGTI (SEQ ID NO: 114), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AISSDSSGTI (SEQ ID NO: 114), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 comprising an amino acid sequence of AISSDSSGTI (SEQ ID NO: 114), and a CDR3 comprising an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0114] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AASGFSFGSFGMS (SEQ ID NO: 107), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGRSTSR (SEQ ID NO: 118). In some embodiments,Attorney Docket No. VRD-024WO1 the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AASGFSFGSFGMS (SEQ ID NO: 107), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGRSTSR (SEQ ID NO: 118). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AASGFSFGSFGMS (SEQ ID NO: 107), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGRSTSR (SEQ ID NO: 118). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of AASGFSFGSFGMS (SEQ ID NO: 107), a CDR2 comprising an amino acid sequence of AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence of TIGRSTSR (SEQ ID NO: 118).

[0115] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AASGFTFGSAGMS (SEQ ID NO: 108), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AASGFTFGSAGMS (SEQ ID NO: 108), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AASGFTFGSAGMS (SEQ ID NO: 108), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of AASGFTFGSAGMS (SEQ ID NO: 108), a CDR2 comprising an amino acid sequence of AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 comprising an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).Attorney Docket No. VRD-024WO1

[0116] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AASGFTFGSFGAS (SEQ ID NO: 109), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AASGFTFGSFGAS (SEQ ID NO: 109), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AASGFTFGSFGAS (SEQ ID NO: 109), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of AASGFTFGSFGAS (SEQ ID NO: 109), a CDR2 comprising an amino acid sequence of AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 comprising an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0117] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGSFG (SEQ ID NO: 119), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from IDSGGTDT (SEQ ID NO: 123), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGSFG (SEQ ID NO: 119), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from IDSGGTDT (SEQ ID NO: 123), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGSFG (SEQ ID NO: 119), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from IDSGGTDT (SEQ ID NO:Attorney Docket No. VRD-024WO1123), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGSFG (SEQ ID NO: 119), a CDR2 comprising an amino acid sequence of IDSGGTDT (SEQ ID NO: 123), and a CDR3 comprising an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0118] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGSFG (SEQ ID NO: 119), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from IDSGGADT (SEQ ID NO: 124), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGRSASR (SEQ ID NO: 116). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGSFG (SEQ ID NO: 119), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from IDSGGADT (SEQ ID NO:124), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGRSASR (SEQ ID NO: 116). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGSFG (SEQ ID NO: 119), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from IDSGGADT (SEQ ID NO:124), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGRSASR (SEQ ID NO: 116). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGSFG (SEQ ID NO: 119), a CDR2 comprising an amino acid sequence of IDSGGADT (SEQ ID NO: 124), and a CDR3 comprising an amino acid sequence of TIGRSASR (SEQ ID NO: 116).

[0119] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGQFG (SEQ ID NO: 120), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from ISSDGSGT (SEQ ID NO:125), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGQFG (SEQ ID NO: 120), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues fromAttorney Docket No. VRD-024WO1ISSDGSGT (SEQ ID NO: 125), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGQFG (SEQ ID NO: 120), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from ISSDGSGT (SEQ ID NO: 125), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGQFG (SEQ ID NO: 120), a CDR2 comprising an amino acid sequence of ISSDGSGT (SEQ ID NO: 125), and a CDR3 comprising an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0120] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGQFG (SEQ ID NO: 120), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from ISSDASGT (SEQ ID NO: 126), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGQFG (SEQ ID NO: 120), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from ISSDASGT (SEQ ID NO: 126), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGQFG (SEQ ID NO: 120), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from ISSDASGT (SEQ ID NO: 126), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGQFG (SEQ ID NO: 120), a CDR2 comprising an amino acid sequence of ISSDASGT (SEQ ID NO: 126), and a CDR3 comprising an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0121] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues fromAttorney Docket No. VRD-024WO1GFTFGQFG (SEQ ID NO: 120), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from ISSDSSGT (SEQ ID NO: 127), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGQFG (SEQ ID NO: 120), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from ISSDSSGT (SEQ ID NO: 127), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGQFG (SEQ ID NO: 120), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from ISSDSSGT (SEQ ID NO: 127), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGQFG (SEQ ID NO: 120), a CDR2 comprising an amino acid sequence of ISSDSSGT (SEQ ID NO: 127), and a CDR3 comprising an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0122] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFSFGSFG (SEQ ID NO: 121), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from IDSGGADT (SEQ ID NO: 124), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGRSTSR (SEQ ID NO: 118). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFSFGSFG (SEQ ID NO: 121), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from IDSGGADT (SEQ ID NO: 124), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGRSTSR (SEQ ID NO: 118). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFSFGSFG (SEQ ID NO: 121), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from IDSGGADT (SEQ ID NO: 124), and a CDR3 comprising an amino acid sequence that differs by no more than 1 aminoAttorney Docket No. VRD-024WO1 acid residue from TIGRSTSR (SEQ ID NO: 118). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFSFGSFG (SEQ ID NO: 121), a CDR2 comprising an amino acid sequence of IDSGGADT (SEQ ID NO: 124), and a CDR3 comprising an amino acid sequence of TIGRSTSR (SEQ ID NO: 118).

[0123] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGSAG (SEQ ID NO: 122), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from IDSGGTDT (SEQ ID NO: 123), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGSAG (SEQ ID NO: 122), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from IDSGGTDT (SEQ ID NO: 123), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGSAG (SEQ ID NO: 122), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from IDSGGTDT (SEQ ID NO: 123), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGSAG (SEQ ID NO: 122), a CDR2 comprising an amino acid sequence of IDSGGTDT (SEQ ID NO: 123), and a CDR3 comprising an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0124] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGSFG (SEQ ID NO: 119), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from IDSGGTDT (SEQ ID NO: 123), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGSFG (SEQ ID NO: 119), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from IDSGGTDT (SEQ ID NO: 123), and a CDR3 comprising an amino acid sequence that differs by no more than 2 aminoAttorney Docket No. VRD-024WO1 acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGSFG (SEQ ID NO: 119), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from IDSGGTDT (SEQ ID NO: 123), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGSFG (SEQ ID NO: 119), a CDR2 comprising an amino acid sequence of IDSGGTDT (SEQ ID NO: 123), and a CDR3 comprising an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0125] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGSF (SEQ ID NO: 128), GFTFGSF (SEQ ID NO: 128), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from DSGGTD (SEQ ID NO: 132), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGSF (SEQ ID NO: 128), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from DSGGTD (SEQ ID NO: 132), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGSF (SEQ ID NO: 128), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from DSGGTD (SEQ ID NO: 132), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGSF (SEQ ID NO: 128), a CDR2 comprising an amino acid sequence of DSGGTD (SEQ ID NO: 132), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0126] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGSF (SEQ ID NO: 128), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from DSGGAD (SEQ ID NO: 133), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 aminoAttorney Docket No. VRD-024WO1 acid residues from GRSASR (SEQ ID NO: 102). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGSF (SEQ ID NO: 128), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from DSGGAD (SEQ ID NO: 133), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GRSASR (SEQ ID NO: 102). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGSF (SEQ ID NO: 128), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from DSGGAD (SEQ ID NO: 133), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GRSASR (SEQ ID NO: 102). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGSF (SEQ ID NO: 128), a CDR2 comprising an amino acid sequence of DSGGAD (SEQ ID NO: 133), and a CDR3 comprising an amino acid sequence of GRSASR (SEQ ID NO: 102).

[0127] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from SSDGSG (SEQ ID NO: 135), SSDGSG (SEQ ID NO: 134), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from SSDGSG (SEQ ID NO: 135), SSDGSG (SEQ ID NO: 134), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from SSDGSG (SEQ ID NO: 135), SSDGSG (SEQ ID NO: 134), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 comprising anAttorney Docket No. VRD-024WO1 amino acid sequence of SSDGSG (SEQ ID NO: 135), SSDGSG (SEQ ID NO: 134), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0128] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from SSDASG, and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from SSDASG, and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from SSDASG, and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence of SSDASG, and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0129] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from SSDSSG (SEQ ID NO: 136), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from SSDSSG (SEQ ID NO: 136), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acidAttorney Docket No. VRD-024WO1 sequence that differs by no more than 1 amino acid residue from SSDSSG (SEQ ID NO: 136), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence of SSDSSG (SEQ ID NO: 136), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0130] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFSFGSF (SEQ ID NO: 130), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from DSGGAD (SEQ ID NO: 133), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GRSTSR (SEQ ID NO: 104). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFSFGSF (SEQ ID NO: 130), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from DSGGAD (SEQ ID NO: 133), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GRSTSR (SEQ ID NO: 104). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFSFGSF (SEQ ID NO: 130), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from DSGGAD (SEQ ID NO: 133), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GRSTSR (SEQ ID NO: 104). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFSFGSF (SEQ ID NO: 130), a CDR2 comprising an amino acid sequence of DSGGAD (SEQ ID NO: 133), and a CDR3 comprising an amino acid sequence of GRSTSR (SEQ ID NO: 104).

[0131] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGSA (SEQ ID NO: 131), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from DSGGTD (SEQ ID NO: 132), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGSA (SEQ ID NO: 131), a CDR2 comprising an amino acid sequenceAttorney Docket No. VRD-024WO1 that differs by no more than 2 amino acid residues from DSGGTD (SEQ ID NO: 132), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGSA (SEQ ID NO: 131), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from DSGGTD (SEQ ID NO: 132), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGSA (SEQ ID NO: 131), a CDR2 comprising an amino acid sequence of DSGGTD (SEQ ID NO: 132), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0132] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GFTFGSF (SEQ ID NO: 128), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from DSGGTD (SEQ ID NO: 132), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GFTFGSF (SEQ ID NO: 128), a CDR2 comprising an amino acid sequence that differs by no more than 2 amino acid residues from DSGGTD (SEQ ID NO: 132), and a CDR3 comprising an amino acid sequence that differs by no more than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GFTFGSF (SEQ ID NO: 128), a CDR2 comprising an amino acid sequence that differs by no more than 1 amino acid residue from DSGGTD (SEQ ID NO: 132), and a CDR3 comprising an amino acid sequence that differs by no more than 1 amino acid residue from GQSTSR (SEQ ID NO: 101). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGSF (SEQ ID NO: 128), a CDR2 comprising an amino acid sequence of DSGGTD (SEQ ID NO: 132), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0133] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of SNTMG (SEQ ID NO: 137), a CDR2 comprising an amino acid sequence of AITWSGGTTYYADSVKG (SEQ ID NO: 138), and a CDR3 comprising an amino acidAttorney Docket No. VRD-024WO1 sequence of EGPKWEPWNGIYHPADFGS (SEQ ID NO: 139). In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of AYPMG (SEQ ID NO: 140), a CDR2 comprising an amino acid sequence of GISWFAGATTDYADSVEG (SEQ ID NO: 141), and a CDR3 comprising an amino acid sequence of SHQLPGGRPGRDMDSYSY (SEQ ID NO: 142).

[0134] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of SYAMG (SEQ ID NO: 143), a CDR2 comprising an amino acid sequence of TINWSGGSTYYADSVKG (SEQ ID NO: 144), and a CDR3 comprising an amino acid sequence of DLYGPGFVLSMEYDY (SEQ ID NO: 145).

[0135] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of SYAMG (SEQ ID NO: 143), a CDR2 comprising an amino acid sequence of VISWSGGSTYYADSVKG (SEQ ID NO: 146), and a CDR3 comprising an amino acid sequence of EGPKWEPYNGIYSPADFGS (SEQ ID NO: 147).

[0136] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GYAMG (SEQ ID NO: 148), a CDR2 comprising an amino acid sequence of AISWFAGDTTDYADSVKG (SEQ ID NO: 149), and a CDR3 comprising an amino acid sequence of SSARPMSGRSDEYHY (SEQ ID NO: 150).

[0137] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of SYVMA (SEQ ID NO: 151), a CDR2 comprising an amino acid sequence of SINWSGGSTYYAHSVKG (SEQ ID NO: 152), and a CDR3 comprising an amino acid sequence of DLYGLGYEVMSYDY (SEQ ID NO: 153).

[0138] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of NYNAG (SEQ ID NO: 154), a CDR2 comprising an amino acid sequence of AINWSGGTTYYADSVKG (SEQ ID NO: 155), and a CDR3 comprising an amino acid sequence of DPDWSILNPREYDY (SEQ ID NO: 156).

[0139] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of TYGMG (SEQ ID NO: 157), a CDR2 comprising an amino acid sequence of AINWKGDRYYADSVKG (SEQ ID NO: 158), and a CDR3 comprising an amino acid sequence of DSDGSAFSRRLEYDY (SEQ ID NO: 159).

[0140] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of GYAMG (SEQ ID NO: 160), a CDR2 comprising an amino acid sequence of AISWFAGDTTDYANSVKG (SEQ ID NO: 161), and a CDR3 comprising an amino acid sequence of SSARPLSSRSDEYHY (SEQ ID NO: 162).Attorney Docket No. VRD-024WO1

[0141] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of HSNMA (SEQ ID NO: 163), a CDR2 comprising an amino acid sequence of HIHWRGSTTYLDSVKG (SEQ ID NO: 164), and a CDR3 comprising an amino acid sequence of DSARRILVTVSTSYDY (SEQ ID NO: 165).

[0142] In some embodiments, the sdAb comprises a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 166), a CDR2 comprising an amino acid sequence of SISGSGSDTLYADSVKG (SEQ ID NO: 167), and a CDR3 comprising an amino acid sequence of GGSLSR (SEQ ID NO: 168).

[0143] In some embodiments, the Fc fusion molecule comprises, from N-terminus to C- terminus, an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y; a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and an sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101). In some embodiments, the Fc fusion molecule comprises, from C-terminus to N- terminus, an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y; a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and an sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0144] In some embodiments, the Fc fusion molecule comprises, from N-terminus to C- terminus, an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F; a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and an sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101). In some embodiments, the Fc fusion molecule comprises, from C-terminus to N-terminus, an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F; a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and an sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising anAttorney Docket No. VRD-024WO1 amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0145] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 1. In some embodiments, the sdAb comprises an amino acid sequence identical to SEQ ID NO: 1.

[0146] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 2. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 2. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 2. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 2. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 2. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 2. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 2. In some embodiments, the sdAb comprises an amino acid sequence identical to SEQ ID NO: 2.

[0147] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 3. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 3. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 3. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 3. In some embodiments, the sdAb comprisesAttorney Docket No. VRD-024WO1 an amino acid sequence at least 97% identical to SEQ ID NO: 3. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 3. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 3. In some embodiments, the sdAb comprises an amino acid sequence identical to SEQ ID NO: 3.

[0148] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 4. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 4. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 4. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 4. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 4. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 4. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 4. In some embodiments, the sdAb comprises an amino acid sequence identical to SEQ ID NO: 4.

[0149] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 5. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 5. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 5. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 5. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 5. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 5. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 5. In some embodiments, the sdAb comprises an amino acid sequence identical to SEQ ID NO: 5.

[0150] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 6. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to SEQ IDAttorney Docket No. VRD-024WO1NO: 6. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 6. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 6. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 6. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 6. In some embodiments, the sdAb comprises an amino acid sequence identical to SEQ ID NO: 6.

[0151] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 7. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 7. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 7. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 7. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 7. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 7. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 7. In some embodiments, the sdAb comprises an amino acid sequence identical to SEQ ID NO: 7.

[0152] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 8. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 8. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 8. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 8. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 8. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 8. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 8. In some embodiments, the sdAb comprises an amino acid sequence identical to SEQ ID NO: 8.Attorney Docket No. VRD-024WO1

[0153] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 9. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 9. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 9. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 9. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 9. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 9. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 9. In some embodiments, the sdAb comprises an amino acid sequence identical to SEQ ID NO: 9.

[0154] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 10. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 10. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 10. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 10. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 10. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 10. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 10. In some embodiments, the sdAb comprises an amino acid sequence identical to SEQ ID NO: 10.

[0155] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 11. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 11. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 11. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 11. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 11. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to SEQ IDAttorney Docket No. VRD-024WO1NO: 11. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 11. In some embodiments, the sdAb comprises an amino acid sequence identical to SEQ ID NO: 11.

[0156] In some embodiments, the sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 1-11 and 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 60% identical to any one of SEQ ID NOs: 1-11 and 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 70% identical to any one of SEQ ID NOs: 1- 11 and 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 80% identical to any one of SEQ ID NOs: 1-11 and 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 1-11 and 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 1-11 and 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 1-11 and 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 1-11 and 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 1-11 and 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 1-11 and 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 1-11 and 169-179. In some embodiments, the sdAb comprises an amino acid sequence identical to any one of SEQ ID NOs: 1-11 and 169-179.

[0157] In some embodiments, the sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 60% identical to any one of SEQ ID NOs: 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 70% identical to any one of SEQ ID NOs: 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 80% identical to any one of SEQ ID NOs: 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 169-179. In some embodiments, the sdAbAttorney Docket No. VRD-024WO1 comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 169- 179. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 169-179. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 169-179. In some embodiments, the sdAb comprises an amino acid sequence identical to any one of SEQ ID NOs: 169-179.

[0158] In some embodiments, the Fc region is modified. In some embodiments, the Fc region is modified to increase binding to FcRn. In some embodiments, the Fc region is modified to increase binding to FcRn at acidic pH. In some embodiments, the Fc region is modified to increase binding to FcRn at physiological pH. In some embodiments, the Fc region is modified to increase binding to FcRn at acidic pH and physiological pH.

[0159] In some embodiments, the Fc region comprises one or more amino acid substitutions at positions 237, 238, 239, 248, 250, 252, 253, 254, 255, 256, 257, 258, 265,270, 272, 286, 288, 289, 297, 298, 303, 305, 307, 308, 309, 311, 312, 314, 315, 317, 325,332, 334, 340, 356, 360, 362, 376, 378, 380, 382, 384, 385, 386, 387, 388, 389, 400, 413,415, 424, 428, 433, 434, 435, 436, 439, or 447, wherein the positions are numbered according to the EU index.

[0160] In some embodiments, the Fc region comprises at least one amino acid substitution. In some embodiments, the Fc region comprises at least two amino acid substitutions. In some embodiments, the Fc region comprises at least three amino acid substitutions. In some embodiments, the Fc region comprises at least four amino acid substitutions. In some embodiments, the Fc region comprises at least five amino acid substitutions. In some embodiments, the Fc region comprises at least six amino acid substitutions. In some embodiments, the Fc region comprises at least seven amino acid substitutions. In some embodiments, the Fc region comprises at least eight amino acid substitutions. In some embodiments, the Fc region comprises at least nine amino acid substitutions. In some embodiments, the Fc region comprises at least ten amino acid substitutions.

[0161] In some embodiments, the Fc region comprises an amino acid substitution at position 237. In some embodiments, the Fc region comprises an amino acid substitution at position 238. In some embodiments, the Fc region comprises an amino acid substitution at position 239. In some embodiments, the Fc region comprises an amino acid substitution atAttorney Docket No. VRD-024WO1 position 248. In some embodiments, the Fc region comprises an amino acid substitution at position 250. In some embodiments, the Fc region comprises an amino acid substitution at position 252. In some embodiments, the Fc region comprises an amino acid substitution at position 253. In some embodiments, the Fc region comprises an amino acid substitution at position 254. In some embodiments, the Fc region comprises an amino acid substitution at position 255. In some embodiments, the Fc region comprises an amino acid substitution at position 256. In some embodiments, the Fc region comprises an amino acid substitution at position 257. In some embodiments, the Fc region comprises an amino acid substitution at position 258.

[0162] In some embodiments, the Fc region comprises an amino acid substitution at position 265. In some embodiments, the Fc region comprises an amino acid substitution at position 270. In some embodiments, the Fc region comprises an amino acid substitution at position 272. In some embodiments, the Fc region comprises an amino acid substitution at position 286. In some embodiments, the Fc region comprises an amino acid substitution at position 288. In some embodiments, the Fc region comprises an amino acid substitution at position 289. In some embodiments, the Fc region comprises an amino acid substitution at position 297. In some embodiments, the Fc region comprises an amino acid substitution at position 298.

[0163] In some embodiments, the Fc region comprises an amino acid substitution at position 303. In some embodiments, the Fc region comprises an amino acid substitution at position 305. In some embodiments, the Fc region comprises an amino acid substitution at position 307. In some embodiments, the Fc region comprises an amino acid substitution at position 308. In some embodiments, the Fc region comprises an amino acid substitution at position 309. In some embodiments, the Fc region comprises an amino acid substitution at position 311. In some embodiments, the Fc region comprises an amino acid substitution at position 312. In some embodiments, the Fc region comprises an amino acid substitution at position 314. In some embodiments, the Fc region comprises an amino acid substitution at position 315. In some embodiments, the Fc region comprises an amino acid substitution at position 317.

[0164] In some embodiments, the Fc region comprises an amino acid substitution at position 325. In some embodiments, the Fc region comprises an amino acid substitution at position 332. In some embodiments, the Fc region comprises an amino acid substitution at position 334. In some embodiments, the Fc region comprises an amino acid substitution atAttorney Docket No. VRD-024WO1 position 340. In some embodiments, the Fc region comprises an amino acid substitution at position 356. In some embodiments, the Fc region comprises an amino acid substitution at position 360. In some embodiments, the Fc region comprises an amino acid substitution at position 362. In some embodiments, the Fc region comprises an amino acid substitution at position 376. In some embodiments, the Fc region comprises an amino acid substitution at position 378.

[0165] In some embodiments, the Fc region comprises an amino acid substitution at position 380. In some embodiments, the Fc region comprises an amino acid substitution at position 382. In some embodiments, the Fc region comprises an amino acid substitution at position 384. In some embodiments, the Fc region comprises an amino acid substitution at position 385. In some embodiments, the Fc region comprises an amino acid substitution at position 386. In some embodiments, the Fc region comprises an amino acid substitution at position 387. In some embodiments, the Fc region comprises an amino acid substitution at position 388. In some embodiments, the Fc region comprises an amino acid substitution at position 389.

[0166] In some embodiments, the Fc region comprises an amino acid substitution at position 400. In some embodiments, the Fc region comprises an amino acid substitution at position 413. In some embodiments, the Fc region comprises an amino acid substitution at position 415. In some embodiments, the Fc region comprises an amino acid substitution at position 424. In some embodiments, the Fc region comprises an amino acid substitution at position 428. In some embodiments, the Fc region comprises an amino acid substitution at position 433. In some embodiments, the Fc region comprises an amino acid substitution at position 434. In some embodiments, the Fc region comprises an amino acid substitution at position 435. In some embodiments, the Fc region comprises an amino acid substitution at position 436. In some embodiments, the Fc region comprises an amino acid substitution at position 439. In some embodiments, the Fc region comprises an amino acid substitution at position 447.

[0167] In some embodiments, the Fc region comprises one or more amino acid substitutions selected from the group consisting of 237M, 238A, 239K, 2481, 250A, 250F, 2501, 250M, 250Q, 250S, 250V, 250W, 250Y, 252F, 252W, 252Y, 254T, 255E, 256D, 256E, 256Q, 257A, 257G, 2571, 257L, 257M, 257N, 257S, 257T, 257V, 258H, 265A, 270F, 286A, 286E, 289H, 297A, 298G, 303A, 305A, 307A, 307D, 307F, 307G, 307H, 3071, 307K, 307L, 307M, 307N, 307P, 307Q, 307R, 307S, 307V, 307W, 307Y, 308A, 308F, 3081, 308L, 308M,Attorney Docket No. VRD-024WO1308P, 308Q, 308T, 309A, 309D, 309E, 309P, 309R, 311A, 311H, 3111, 31 IK, 312A, 312H, 314K, 314R, 315A, 315H, 317A, 325G, 332V, 334L, 360H, 376A, 378V, 380A, 382A, 384A, 385D, 385H, 386P, 387E, 389A, 389S, 424A, 428 A, 428D, 428F, 428G, 428H, 4281, 428K, 428L, 428N, 428P, 428Q, 428S, 428T, 428V, 428W, 428Y, 433K, 433R, 434A, 434F, 434H, 434S, 434W, 434Y, 436H, 4361, and 436F, wherein the positions are numbered according to the EU index.

[0168] In some embodiments, the Fc region comprises an amino acid substitution of 237M. In some embodiments, the Fc region comprises an amino acid substitution of 238A. In some embodiments, the Fc region comprises an amino acid substitution of 239K. In some embodiments, the Fc region comprises an amino acid substitution of 2481.

[0169] In some embodiments, the Fc region comprises an amino acid substitution of 250A. In some embodiments, the Fc region comprises an amino acid substitution of 250F. In some embodiments, the Fc region comprises an amino acid substitution of 2501. In some embodiments, the Fc region comprises an amino acid substitution of 250M. In some embodiments, the Fc region comprises an amino acid substitution of 250Q. In some embodiments, the Fc region comprises an amino acid substitution of 250S. In some embodiments, the Fc region comprises an amino acid substitution of 250V. In some embodiments, the Fc region comprises an amino acid substitution of 250W. In some embodiments, the Fc region comprises an amino acid substitution of 250Y.

[0170] In some embodiments, the Fc region comprises an amino acid substitution of 252F. In some embodiments, the Fc region comprises an amino acid substitution of 252W. In some embodiments, the Fc region comprises an amino acid substitution of 252Y. In some embodiments, the Fc region comprises an amino acid substitution of 254T. In some embodiments, the Fc region comprises an amino acid substitution of 255E. In some embodiments, the Fc region comprises an amino acid substitution of 256D. In some embodiments, the Fc region comprises an amino acid substitution of 256E. In some embodiments, the Fc region comprises an amino acid substitution of 256Q.

[0171] In some embodiments, the Fc region comprises an amino acid substitution of 257A. In some embodiments, the Fc region comprises an amino acid substitution of 257G. In some embodiments, the Fc region comprises an amino acid substitution of 2571. In some embodiments, the Fc region comprises an amino acid substitution of 257L. In some embodiments, the Fc region comprises an amino acid substitution of 257M. In some embodiments, the Fc region comprises an amino acid substitution of 257N. In someAttorney Docket No. VRD-024WO1 embodiments, the Fc region comprises an amino acid substitution of 257S. In some embodiments, the Fc region comprises an amino acid substitution of 257T. In some embodiments. In some embodiments, the Fc region comprises an amino acid substitution of the Fc region comprises an amino acid substitution of 257V. In some embodiments, the Fc region comprises an amino acid substitution of 258H.

[0172] In some embodiments, the Fc region comprises an amino acid substitution of 265A. In some embodiments, the Fc region comprises an amino acid substitution of 270F. In some embodiments, the Fc region comprises an amino acid substitution of 286A. In some embodiments, the Fc region comprises an amino acid substitution of 286E. In some embodiments, the Fc region comprises an amino acid substitution of 289H. In some embodiments, the Fc region comprises an amino acid substitution of 297A. In some embodiments, the Fc region comprises an amino acid substitution of 298G. In some embodiments, the Fc region comprises an amino acid substitution of 303 A. In some embodiments, the Fc region comprises an amino acid substitution of 305A.

[0173] In some embodiments, the Fc region comprises an amino acid substitution of 307A. In some embodiments, the Fc region comprises an amino acid substitution of 307D. In some embodiments, the Fc region comprises an amino acid substitution of 307F. In some embodiments, the Fc region comprises an amino acid substitution of 307G. In some embodiments, the Fc region comprises an amino acid substitution of 307H. In some embodiments, the Fc region comprises an amino acid substitution of 3071. In some embodiments, the Fc region comprises an amino acid substitution of 307K. In some embodiments, the Fc region comprises an amino acid substitution of 307L. In some embodiments, the Fc region comprises an amino acid substitution of 307M. In some embodiments, the Fc region comprises an amino acid substitution of 307N. In some embodiments, the Fc region comprises an amino acid substitution of 307P. In some embodiments, the Fc region comprises an amino acid substitution of 307Q. In some embodiments, the Fc region comprises an amino acid substitution of 307R. In some embodiments, the Fc region comprises an amino acid substitution of 307S. In some embodiments, the Fc region comprises an amino acid substitution of 307V. In some embodiments, the Fc region comprises an amino acid substitution of 307W. In some embodiments, the Fc region comprises an amino acid substitution of 307Y.

[0174] In some embodiments, the Fc region comprises an amino acid substitution of 308A. In some embodiments, the Fc region comprises an amino acid substitution of 308F. InAttorney Docket No. VRD-024WO1 some embodiments, the Fc region comprises an amino acid substitution of 3081. In some embodiments, the Fc region comprises an amino acid substitution of 308L. In some embodiments, the Fc region comprises an amino acid substitution of 308M. In some embodiments, the Fc region comprises an amino acid substitution of 308P. In some embodiments, the Fc region comprises an amino acid substitution of 308Q. In some embodiments, the Fc region comprises an amino acid substitution of 308T. In some embodiments, the Fc region comprises an amino acid substitution of 309A. In some embodiments, the Fc region comprises an amino acid substitution of 309D. In some embodiments, the Fc region comprises an amino acid substitution of 309E. In some embodiments, the Fc region comprises an amino acid substitution of 309P. In some embodiments, the Fc region comprises an amino acid substitution of 309R.

[0175] In some embodiments, the Fc region comprises an amino acid substitution of 311 A. In some embodiments, the Fc region comprises an amino acid substitution of 311H. In some embodiments, the Fc region comprises an amino acid substitution of 31 II. In some embodiments, the Fc region comprises an amino acid substitution of 31 IK. In some embodiments, the Fc region comprises an amino acid substitution of 312A. In some embodiments, the Fc region comprises an amino acid substitution of 312H. In some embodiments, the Fc region comprises an amino acid substitution of 314K. In some embodiments, the Fc region comprises an amino acid substitution of 314R.

[0176] In some embodiments, the Fc region comprises an amino acid substitution of 315A. In some embodiments, the Fc region comprises an amino acid substitution of 315H. In some embodiments, the Fc region comprises an amino acid substitution of 317A. In some embodiments, the Fc region comprises an amino acid substitution of 325G. In some embodiments, the Fc region comprises an amino acid substitution of 332V. In some embodiments, the Fc region comprises an amino acid substitution of 334L. In some embodiments, the Fc region comprises an amino acid substitution of 360H. In some embodiments, the Fc region comprises an amino acid substitution of 376A. In some embodiments, the Fc region comprises an amino acid substitution of 378V.

[0177] In some embodiments, the Fc region comprises an amino acid substitution of 380A. In some embodiments, the Fc region comprises an amino acid substitution of 382A. In some embodiments, the Fc region comprises an amino acid substitution of 384A. In some embodiments, the Fc region comprises an amino acid substitution of 385D. In some embodiments, the Fc region comprises an amino acid substitution of 385H. In someAttorney Docket No. VRD-024WO1 embodiments, the Fc region comprises an amino acid substitution of 386P. In some embodiments, the Fc region comprises an amino acid substitution of 387E. In some embodiments, the Fc region comprises an amino acid substitution of 389A. In some embodiments, the Fc region comprises an amino acid substitution of 389S. In some embodiments, the Fc region comprises an amino acid substitution of 424A.

[0178] In some embodiments, the Fc region comprises an amino acid substitution of 428A. In some embodiments, the Fc region comprises an amino acid substitution of 428D. In some embodiments, the Fc region comprises an amino acid substitution of 428F. In some embodiments, the Fc region comprises an amino acid substitution of 428G. In some embodiments, the Fc region comprises an amino acid substitution of 428H. In some embodiments, the Fc region comprises an amino acid substitution of 4281. In some embodiments, the Fc region comprises an amino acid substitution of 428K. In some embodiments, the Fc region comprises an amino acid substitution of 428L. In some embodiments, the Fc region comprises an amino acid substitution of 428N. In some embodiments, the Fc region comprises an amino acid substitution of 428P. In some embodiments, the Fc region comprises an amino acid substitution of 428Q. In some embodiments, the Fc region comprises an amino acid substitution of 428S. In some embodiments, the Fc region comprises an amino acid substitution of 428T. In some embodiments, the Fc region comprises an amino acid substitution of 428V. In some embodiments, the Fc region comprises an amino acid substitution of 428W. In some embodiments, the Fc region comprises an amino acid substitution of 428Y.

[0179] In some embodiments, the Fc region comprises an amino acid substitution of 433K. In some embodiments, the Fc region comprises an amino acid substitution of 433R. In some embodiments, the Fc region comprises an amino acid substitution of 434A. In some embodiments, the Fc region comprises an amino acid substitution of 434F. In some embodiments, the Fc region comprises an amino acid substitution of 434H. In some embodiments, the Fc region comprises an amino acid substitution of 434S. In some embodiments, the Fc region comprises an amino acid substitution of 434W. In some embodiments, the Fc region comprises an amino acid substitution of 434Y. In some embodiments, the Fc region comprises an amino acid substitution of 436H. In some embodiments, the Fc region comprises an amino acid substitution of 4361. In some embodiments, the Fc region comprises an amino acid substitution of 436F.Attorney Docket No. VRD-024WO1

[0180] In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 433, and / or 434. In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 428, 433, and / or 434. In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 428, and / or 434.

[0181] In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and 434, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 433, and 434. In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 428, 433, and 434. In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 428, and 434.

[0182] In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and / or 434F, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and / or 434Y. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433R, and / or 434Y. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433R, and / or 434F. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and / or 434F. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and / or 434Y. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433R, and / or 434F. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, and / or 434F.

[0183] In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434F, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433R, and 434Y. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433R, and 434F. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L,Attorney Docket No. VRD-024WO1433K, and 434F. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434Y. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433R, and 434F. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, and 434F.

[0184] In some embodiments, the Fc region described herein comprises an amino acid sequence at least 70% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the Fc region described herein comprises an amino acid sequence at least 75% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the Fc region described herein comprises an amino acid sequence at least 80% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the Fc region described herein comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the Fc region described herein comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the Fc region described herein comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the Fc region described herein comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the Fc region described herein comprises an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the Fc region described herein comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the Fc region described herein comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the Fc region described herein comprises an amino acid sequence identical to any one of SEQ ID NOs: 13-38.

[0185] In some embodiments, the Fc fusion molecule comprises, from N-terminus to C- terminus, the Fc region, the linker, and the sdAb. In some embodiments, the Fc fusion molecule comprises, from C-terminus to N-terminus, the Fc region, the linker, and the sdAb.

[0186] In some embodiments, the albumin or albumin binding domain is fused to the Fc region. In some embodiments, the albumin or albumin binding domain is fused to the C- terminus of the Fc region. In some embodiments, the anti-HSA sdAb is fused to the C- terminus of the Fc region. In some embodiments, the albumin or albumin binding domain is fused to the N-terminus of the Fc region. In some embodiments, the anti-HSA sdAb is fused to the N-terminus of the Fc region.Attorney Docket No. VRD-024WO1

[0187] In some embodiments, the Fc fusion molecule comprises two Fc regions. In some embodiments, the Fc fusion molecule comprises one or more albumin. In some embodiments, the Fc fusion molecule comprises one or more albumin binding domains. In some embodiments, the Fc fusion molecule comprises two Fc regions and one anti-HSA sdAb.

[0188] In some embodiments, the Fc fusion molecule is a homodimer. In some embodiments, the Fc fusion molecule is a heterodimer. In some embodiments, the heterodimer comprises a first polypeptide comprising a first Fc region, a linker, and an albumin, and a second polypeptide comprising a second Fc region. In some embodiments, the heterodimer comprises a first polypeptide comprising a first Fc region, a linker, and an albumin binding domain, and a second polypeptide comprising a second Fc region. In some embodiments, the heterodimer comprises a first polypeptide comprising a first Fc region, a linker, and an anti-HSA sdAb, and a second polypeptide comprising a second Fc region.

[0189] In some embodiments, the Fc region further comprises “knob-in-to-hole” mutations. In some embodiments, the first Fc region further comprises the amino acid substitutions of Y349C, T366S, L368A, and Y407V, and the second Fc region further comprises the amino acid substitutions of S354C and T366W. In some embodiments, the first Fc region further comprises the amino acid substitutions of T366S, L368A, and Y407V, and the second Fc region further comprises the amino acid substitution of T366W.

[0190] In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 70% identical to any one of SEQ ID NOs: 43-67 or 70-90. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 75% identical to any one of SEQ ID NOs: 43-67 or 70-90. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 80% identical to any one of SEQ ID NOs: 43-67 or 70-90. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 43-67 or 70-90. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 43-67 or 70-90. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 43-67 or 70-90. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 43-67 or 70-90. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 43-67 or 70-90. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 43-67 or 70-90. In someAttorney Docket No. VRD-024WO1 embodiments, the Fc fusion molecule comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 43-67 or 70-90. In some embodiments, the Fc fusion molecule comprises an amino acid sequence identical to any one of SEQ ID NOs: 43-67 or 70-90.

[0191] In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 70% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 75% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 80% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 85% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 90% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 95% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 96% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 97% identical to SEQ ID NO:55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 98% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 99% identical to SEQ ID NO: 55. In some embodiments, the Fc fusion molecule comprises an amino acid sequence identical to SEQ ID NO: 55.

[0192] In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 70% identical to SEQ ID NO: 56. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 75% identical to SEQ ID NO: 56. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 80% identical to SEQ ID NO: 56. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 85% identical to SEQ ID NO: 56. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 90% identical to SEQ ID NO: 56. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 95% identical to SEQ ID NO: 56. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 96% identical to SEQ ID NO: 56. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 97% identical to SEQ ID NO:56. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 98% identical to SEQ ID NO: 56. In some embodiments, the Fc fusion molecule comprisesAttorney Docket No. VRD-024WO1 an amino acid sequence at least 99% identical to SEQ ID NO: 56. In some embodiments, the Fc fusion molecule comprises an amino acid sequence identical to SEQ ID NO: 56.

[0193] In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 70% identical to SEQ ID NO: 58. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 75% identical to SEQ ID NO: 58. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 80% identical to SEQ ID NO: 58. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 85% identical to SEQ ID NO: 58. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 90% identical to SEQ ID NO: 58. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 95% identical to SEQ ID NO: 58. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 96% identical to SEQ ID NO: 58. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 97% identical to SEQ ID NO:58. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 98% identical to SEQ ID NO: 58. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 99% identical to SEQ ID NO: 58. In some embodiments, the Fc fusion molecule comprises an amino acid sequence identical to SEQ ID NO: 58.

[0194] In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 70% identical to SEQ ID NO: 59. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 75% identical to SEQ ID NO: 59. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 80% identical to SEQ ID NO: 59. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 85% identical to SEQ ID NO: 59. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 90% identical to SEQ ID NO: 59. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 95% identical to SEQ ID NO: 59. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 96% identical to SEQ ID NO: 59. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 97% identical to SEQ ID NO:59. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 98% identical to SEQ ID NO: 59. In some embodiments, the Fc fusion molecule comprises an amino acid sequence at least 99% identical to SEQ ID NO: 59. In some embodiments, the Fc fusion molecule comprises an amino acid sequence identical to SEQ ID NO: 59.Attorney Docket No. VRD-024WO1

[0195] In some embodiments, the Fc region further comprises a lysine residue at the C- terminus.

[0196] In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule once every week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, once every eight weeks, or once every ten weeks. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule once every week. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule once every two weeks. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule once every three weeks. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule once every four weeks. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule once every five weeks. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule once every six weeks. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule once every seven weeks. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule once every eight weeks. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule once every ten weeks.

[0197] In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 0.5 mg / kg to 50 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 1 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 2.5 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 4 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 5 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 8 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 10 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 12 mg / kg. In some embodiments, the therapeutically effectiveAttorney Docket No. VRD-024WO1 dosing regimen comprises administering the Fc fusion molecule at a dose of 16 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 20 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 24 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 28 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 32 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 36 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 40 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 44 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 48 mg / kg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 50 mg / kg.

[0198] In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of between 2.5 mg to 7500 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 175 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 225 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 275 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 350 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 425 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 500 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 600 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 700 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 1000 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 1250 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering theAttorney Docket No. VRD-024WO1Fc fusion molecule at a dose of 1400 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 1700 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 2000 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 2400 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 2800 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 3200 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 3500 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 4000 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 4500 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 5000 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 5500 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 6000 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 6500 mg. In some embodiments, the therapeutically effective dosing regimen comprises administering the Fc fusion molecule at a dose of 7000 mg.

[0199] In some embodiments, the disease or disorder is an autoimmune disorder. In some embodiments, the disease or disorder is an inflammatory disorder. In some embodiments, the disease or disorder is an ocular disorder.

[0200] In some embodiments, the disease or disorder is generalized myasthenia gravis (gMG), Grave's disease, chronic inflammatory demyelinating polyneuropathy, myositis, autoimmune encephalitis, myelin oligodendrocyte glycoprotein antibody disorders (MOG- antibody disorder), membranous nephropathy, lupus nephritis, thyroid eye disease, warm autoimmune hemolytic anemia, hemolytic disease of the fetus and newborn, idiopathic inflammatory myopathy, idiopathic thrombocytopenic purpura, primary Sjogren’s Syndrome, systemic lupus erythematosus, rheumatoid arthritis, bullous pemphigoid, pemphigus foliaceus, pemphigus vulgaris, or cutaneous lupus erythematosus, antibody mediated rejection, systemic sclerosis, lupus neuropathy, or ocular myasthenia gravis.Attorney Docket No. VRD-024WO1

[0201] In some embodiments, the disease or disorder is generalized myasthenia gravis (gMG). In some embodiments, the disease or disorder is Grave's disease. In some embodiments, the disease or disorder is chronic inflammatory demyelinating polyneuropathy. In some embodiments, the disease or disorder is myositis. In some embodiments, the disease or disorder is autoimmune encephalitis. In some embodiments, the disease or disorder is myelin oligodendrocyte glycoprotein antibody disorder (MOG-antibody disorder). In some embodiments, the disease or disorder is membranous nephropathy. In some embodiments, the disease or disorder is lupus nephritis. In some embodiments, the disease or disorder is thyroid eye disease. In some embodiments, the disease or disorder is warm autoimmune hemolytic anemia. In some embodiments, the disease or disorder is hemolytic disease of the fetus and newborn. In some embodiments, the disease or disorder is an idiopathic inflammatory myopathy. In some embodiments, the disease or disorder is idiopathic thrombocytopenic purpura. In some embodiments, the disease or disorder is primary Sjogren’s Syndrome. In some embodiments, the disease or disorder is systemic lupus erythematosus. In some embodiments, the disease or disorder is rheumatoid arthritis. In some embodiments, the disease or disorder is bullous pemphigoid. In some embodiments, the disease or disorder is pemphigus foliaceus. In some embodiments, the disease or disorder is pemphigus vulgaris. In some embodiments, the disease or disorder is cutaneous lupus erythematosus. In some embodiments, the disease or disorder is antibody mediated rejection. In some embodiments, the disease or disorder is systemic sclerosis. In some embodiments, the disease or disorder is lupus neuropathy. In some embodiments, the disease or disorder is ocular myasthenia gravis.

[0202] In some embodiments, the disease or disorder is associated with elevated levels of an IgG.

[0203] In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 90%, to less than 85%, to less than 80%, to less than 75%, to less than 70%, to less than 65%, to less than 60%, to less than 50%, to less than 55%, to less than 40%, to less than 30%, or to less than 25% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 90%, to less than 85%, to less than 80%, to less than 75%, to less than 70%, to less than 65%, to less than 60%, to less than 50%, to less than 55%, to less than 40%, to less than 30%, or to less than 25% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days post administration. In some embodiments,Attorney Docket No. VRD-024WO1 administering the Fc fusion molecule reduces IgG level to less than 90%, to less than 85%, to less than 80%, to less than 75%, to less than 70%, to less than 65%, to less than 60%, to less than 50%, to less than 55%, to less than 40%, to less than 30%, or to less than 25% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 7 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 90%, to less than 85%, to less than 80%, to less than 75%, to less than 70%, to less than 65%, to less than 60%, to less than 50%, to less than 55%, to less than 40%, to less than 30%, or to less than 25% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 10 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 90%, to less than 85%, to less than 80%, to less than 75%, to less than 70%, to less than 65%, to less than 60%, to less than 50%, to less than 55%, to less than 40%, to less than 30%, or to less than 25% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 15 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 90%, to less than 85%, to less than 80%, to less than 75%, to less than 70%, to less than 65%, to less than 60%, to less than 50%, to less than 55%, to less than 40%, to less than 30%, or to less than 25% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 20 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 90%, to less than 85%, to less than 80%, to less than 75%, to less than 70%, to less than 65%, to less than 60%, to less than 50%, to less than 55%, to less than 40%, to less than 30%, or to less than 25% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 25 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 90%, to less than 85%, to less than 80%, to less than 75%, to less than 70%, to less than 65%, to less than 60%, to less than 50%, to less than 55%, to less than 40%, to less than 30%, or to less than 25% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 30 days post administration.

[0204] In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 90% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 85% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days postAttorney Docket No. VRD-024WO1 administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 80% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration.

[0205] In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 75% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 70% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 65% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 60% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration.

[0206] In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 55% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 50% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 45% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 40% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 35% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgGAttorney Docket No. VRD-024WO1 level to less than 30% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration. In some embodiments, administering the Fc fusion molecule reduces IgG level to less than 25% as compared to an IgG level prior to the administration of the Fc fusion molecule, for at least 5 days, 7 days, 10 days, 15 days, 20 days, 25 days, or 30 days post administration.

[0207] In some embodiments, the half-life of the Fc fusion molecule is greater than the half-life of efgartifimod. In some embodiments, the half-life of the Fc fusion molecule is at least 2-fold greater than the half-life of efgartifimod. In some embodiments, the half-life of the Fc fusion molecule is at least 3-fold greater than the half-life of efgartifimod. In some embodiments, the half-life of the Fc fusion molecule is at least 5-fold greater than the halflife of efgartifimod. In some embodiments, the half-life of the Fc fusion molecule is longer than the Fc region alone.

[0208] In one aspect, the present invention provides, among other things, a method for formulating a composition for treating a disease or disorder, wherein the composition comprises a therapeutically effective dose of the Fc fusion molecule described herein.

[0209] In one aspect, the present invention provides, among other things, a kit comprising the Fc fusion molecule described herein and instructions for reducing an IgG level. In one aspect, the present invention provides, among other things, a kit comprising the Fc fusion molecule described herein and instructions for treating a disease or disorder. In some embodiments, the instructions comprise administering the Fc fusion molecule according to the methods described herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0210] The drawings are for illustration purposes only, and are not meant to be limiting.

[0211] FIG. 1 are exemplary graphs demonstrating the effects of exemplary Fc fusion molecules on IgG reduction up to 14 days post-administration in a cynomolgus monkey model.

[0212] FIG. 2 is an exemplary graph illustrating the serum half-life of Fc fusion molecules up to 14 days post-administration in a cynomolgus monkey model.

[0213] FIG. 3 are exemplary graphs visualizing the changes in albumin up to 14 days post-administration of exemplary Fc fusion molecules in a cynomolgus monkey model.Attorney Docket No. VRD-024WO1

[0214] FIG. 4 are exemplary graphs showing the changes in low density lipoprotein (LDL) up to 14 days post-administration of exemplary Fc fusion molecules in a cynomolgus monkey model.

[0215] FIG. 5 is a series of exemplary graphs demonstrating the effects of exemplary Fc fusion molecules on IgG reduction up to 42 days post-administration in a cynomolgus monkey model.

[0216] FIG. 6 is a series of exemplary graphs illustrating the serum half-life of exemplary Fc fusion molecules up to 42 days post-administration in a cynomolgus monkey model.

[0217] FIG. 7 is a series of exemplary graphs visualizing the changes in albumin up to 42 days post-administration of exemplary Fc fusion molecules in a cynomolgus monkey model.

[0218] FIG. 8 is a series of exemplary graphs showing the changes in low density lipoprotein (LDL) up to 42 days post-administration of exemplary Fc fusion molecules in a cynomolgus monkey model.

[0219] FIG. 9 is a series of exemplary graphs showing the serum concentrations of an exemplary Fc fusion molecule after subcutaneous (SC) or intravenous (IV) administration of a first dose in a cynomolgus monkey model.

[0220] FIG 10 is an exemplary graph demonstrating the IgG reduction after repeated SC or IV administration of an exemplary Fc fusion molecule in a cynomolgus monkey model.

[0221] FIG. 11 is an exemplary graph showing the changes in serum albumin relative to a baseline in cynomolgus monkeys after repeated SC or IV administration of an exemplary Fc fusion molecule.

[0222] FIG. 12 is an exemplary graph showing the changes in LDL relative to a baseline in cynomolgus monkeys after repeated SC or IV administration of an exemplary Fc fusion molecule.

[0223] FIG. 13 is an exemplary graph showing the serum concentrations of exemplary Fc fusion molecule after SC or IV administration of a first dose in a cynomolgus monkey model.

[0224] FIG 14 is an exemplary graph demonstrating the IgG reduction after repeated SC or IV administration of exemplary Fc fusion molecules in a cynomolgus monkey model.

[0225] FIG. 15 is an exemplary graph showing the changes in serum albumin relative to a baseline in cynomolgus monkeys after repeated SC or IV administration of exemplary Fc fusion molecules.Attorney Docket No. VRD-024WO1

[0226] FIG. 16 is an exemplary graph showing the changes in LDL relative to a baseline in cynomolgus monkeys after repeated SC or IV administration of exemplary Fc fusion molecules.

[0227] FIGs. 17A and 17B are exemplary graphs showing the serum concentrations of exemplary Fc fusion molecules after IV administration in a cynomolgus monkey model. FIG. 17A shows the serum concentration for all test articles, and FIG. 17B shows the serum concentrations for individual Fc fusion molecules at different doses.

[0228] FIG 18 is an exemplary graph demonstrating the IgG reduction after IV administration of exemplary Fc fusion molecules at different doses in a cynomolgus monkey model.

[0229] FIG. 19 is an exemplary graph showing the changes in serum albumin relative to a baseline in cynomolgus monkeys after IV administration of exemplary Fc fusion molecules at different doses.

[0230] FIG. 20 is an exemplary graph showing the changes in LDL relative to a baseline in cynomolgus monkeys after IV administration of exemplary Fc fusion molecules at different doses.

[0231] FIG. 21 is an exemplary graph showing PK / PD modeling of an exemplary Fc fusion molecule at 48 mg / kg once every four weeks in human.

[0232] FIG. 22 is an exemplary schematic of a target-mediated drug disposition (TMDD)- IgG model used to predict human PK / PD of an exemplary Fc fusion molecule, Fusion F.

[0233] FIG. 23 is a series of exemplary graphs with non-human primate PK and PD data overlay ed with the TMDD-IgG model.

[0234] FIG. 24 is a series of exemplary graphs showing the predicted human serum concentration and IgG suppression over time after IV administration of an exemplary Fc fusion molecule, Fusion F, at a single dose of 0.2, 2, 10, 25, or 50 mg / kg.

[0235] FIGs. 25A and 25B are exemplary graphs showing the predicted human serum concentration and IgG suppression over time after SC administration of an exemplary Fc fusion molecule, Fusion F, at a single dose of 300, 600, 1200, 2400, or 3000 mg. FIG. 25A shows the model output assuming 65% bioavailability and slow absorption. FIG. 25B shows the model output assuming 75% bioavailability and slow absorption.

[0236] FIGs. 26A, 26B, and 26C are exemplary graphs showing the predicted human serum concentration and IgG suppression over time after SC administration of an exemplary Fc fusion molecule, Fusion F, with repeated doses of 300, 600, 1200, 2400, or 3000 mg. FIG.Attorney Docket No. VRD-024WO126A shows the model output of Q2W administration of 300, 600, 1200, 2400, or 3000 mg Fusion F, assuming 65% bioavailability with slow absorption. FIG. 26B shows the model output of Q4W administration of 300, 600, 1200, 2400, or 3000 mg Fusion F, assuming 65% bioavailability with slow absorption. FIG. 26C shows the model output for 2-dose Q4W administration of Fusion F at 2400 or 3000 mg, assuming 75% bioavailability with slow absorption.

[0237] FIG. 27 shows an exemplary schematic for a first-in-human assessment of an exemplary Fc fusion molecule.DEFINITIONS

[0238] In order for the present disclosure to be more readily understood, certain terms are first defined below. Additional definitions for the following terms and other terms are set forth throughout the specification.

[0239] Any numerical values used in this application are meant to cover any variations within the standard deviation or normal fluctuations appreciated by one of ordinary skill in the relevant art.

[0240] Antibody. As used herein, the term “antibody” refers to immunoglobulin molecules and immunologically active portions of immunoglobulin (Ig) molecules, i.e., molecules that contain an antigen binding site that binds (immunoreacts with) an antigen. By “binds” or “immunoreacts with” is meant that the antibody reacts with one or more antigenic determinants of the desired target. Antibodies include antibody fragments. Antibodies also include, but are not limited to, polyclonal, monoclonal, chimeric domain antibody, single chain, Fab, Fab’, F(ab’)2 fragments, scFvs, single-domain antibodies (sdAb). An antibody may be a whole antibody, or immunoglobulin, or an antibody fragment.

[0241] Acidic pH. As used herein, the term “acidic pH” refers to a pH that is less than a physiological pH. Acidic pH may also be used to describe the pH in endosomes or lysosomes. In some embodiments, acidic pH refers to a pH range of 4.5-6.8. In some embodiments, acidic pH refers to a pH range of 4.8-6.8. In some embodiments, acidic pH refers to a pH range of 4.8-6.0. In some embodiments, acidic pH refers to a pH range of 6.0- 6.8. In some embodiments, acidic pH refers to a pH of 6.0.

[0242] Physiological pH: As used herein, the term “physiological pH” refers to the pH that is outside the endosome. In some embodiments, physiological pH refers to the normalAttorney Docket No. VRD-024WO1 range of pH levels in the body’s essential fluids and tissues. In some embodiments, physiological pH is slightly alkaline. In some embodiments, physiological pH is between 7.0 and 7.8. In some embodiments, physiological pH is between 7.2 and 7.6. In some embodiments, physiological pH is between 7.3 and 7.5. In some embodiments, physiological pH is between 7.35 and 7.45. In some embodiments, physiological pH is 7.4.

[0243] CDRs'. As used herein, the term “CDR” refers to complementarity determining regions of an antibody or antigen binding fragment thereof. The CDRs are three flexible loops within a variable domain of an antibody that fold into specific structures in order to target and / or bind specific antigens. In some embodiments, the sdAbs described herein comprise 3 CDRs: a CDR1, a CDR2, and a CDR3. In some embodiments, the CDR sequences are determined by Kabat, IMGT, Chothia, or North conventions known in the art.

[0244] Knob-in-to-hole mutations'. As used herein, the term “knob-in-to-hole mutations”, “knob mutations”, and “hole mutations” refer to mutations made to promote associations of the Fc regions to an Fc domain. In some embodiments, one or more “knob mutations” are made in a first Fc region by introducing one or more bulky amino acids, and “hole mutations” are made in a second Fc region by introducing one or more smaller amino acids in corresponding positions.

[0245] Fc region'. As used herein, the term “Fc region” refers to a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions. In some embodiments, a human IgG heavy chain Fc region extends from Cys226, or from Pro230, or from Asp221, to the carboxyl-terminus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. In some embodiments, the Fc region is also referred to as an Fc domain, Fc polypeptide, or Fc dimer. In some embodiments, the Fc region comprises the CH2 and CH3 domains of an IgG. In some embodiments, the Fc region comprises the hinge, CH2, and CH3 domains of an IgG. Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991.

[0246] Fusion molecule'. As used herein, the term “fusion molecule” refers to two or more polypeptides in association. In some embodiments, a fusion molecule refers to two or more polypeptides joined together by a linker. In some embodiments, a fusion molecule includesAttorney Docket No. VRD-024WO1 an Fc region and a second protein. In some embodiments, a fusion molecule includes an Fc region and an albumin binding domain. In some embodiments, a fusion molecule includes a protein dimer formed by, for example and without limitation, (1) a first Fc region linked to an albumin binding domain and (2) a second Fc region.

[0247] KD AS used herein, the term “KD”, as used herein, refers to the dissociation constant of a particular antibody-antigen interaction as is known in the art, and would apply as a parameter of the binding affinity of a targeting moiety to its cognate ligand for the subject compositions.

[0248] sdAb As used herein, the term “sdAb” refers to a single domain antibody. Other terms for sdAb include, but are not limited to, domain antibody, VHH, VNAR, or nanobody. An sdAb is a kind of antibody fragment comprising a single monomeric variable antibody domain comprising a CDR1, CDR2, and CDR3. In some embodiments, the sdAb does not comprise a light chain, a constant domain, or an Fc region. However, the sdAbs described herein may be used in any other antibody formats as a variable domain.

[0249] In vitro'. As used herein, the term “zzz vitro" refers to events that occur in an artificial environment, e.g., in a test tube or reaction vessel, in cell culture, etc., rather than within a multi-cellular organism.

[0250] In vivo'. As used herein, the term “z z vivo” refers to events that occur within a multi-cellular organism, such as a human and a non-human animal. In the context of cellbased systems, the term may be used to refer to events that occur within a living cell (as opposed to, for example, in vitro systems).

[0251] Identity'. As used herein, the term “identity” refers a relationship between the sequences of two or more polypeptide molecules or two or more nucleic acid molecules as known in the art, comparing the sequences of these molecules. The relationship determined by doing. In the art, “identity” also means the degree of sequence relatedness between nucleic acid molecules or polypeptides, and in some cases more than one nucleotide sequence or more than one. It may be determined by a match between amino acid sequence strings. “Identity” means between a gap alignment (if any) addressed by a particular mathematical model or computer program (i.e., an “algorithm”) and a smaller sequence of two or more sequences. Measure the percent identity match.

[0252] Treating'. As used herein, the term “treat,” “treatment,” or “treating” refers to any method used to partially or completely alleviate, ameliorate, relieve, inhibit, prevent, delay onset of, reduce severity of and / or reduce incidence of one or more symptoms or features of aAttorney Docket No. VRD-024WO1 particular disease, disorder, and / or condition. Treatment may be administered to a subject who does not exhibit signs of a disease and / or exhibits only early signs of the disease for the purpose of decreasing the risk of developing pathology associated with the disease.DETAILED DESCRIPTION

[0253] The present invention provides, among other things, a method for treating a disease or disorder comprising administering an Fc fusion molecule that binds to neonatal Fc receptor (FcRn) at a therapeutically effective dosing regimen. The method described herein allows, among other things, (1) more durable IgG suppression while maintaining safety profile of an Fc fragment; (2) less frequent administration of the Fc fusion molecule; and / or (3) less frequent, self-administered subcutaneous injection. The methods described herein can be useful in reducing IgG concentrations in a patient, thereby treating, in some embodiments, autoimmune disorders or other disorders with pathology associated with elevated IgG activity.Fc Fusion Molecules

[0254] Described herein, in certain embodiments, are Fc fusion molecules that bind neonatal Fc receptor (FcRn). In some embodiments, the Fc fusion molecule comprises a Fc region. In some embodiments, the Fc fusion molecule comprises a modified Fc region. In some embodiments, the Fc fusion molecule comprises an Fc region and an albumin binding domain. In some embodiments, the Fc fusion molecule has increased half-life as compared to the Fc region alone.

[0255] Described herein, in certain embodiments, the Fc fusion molecule comprises a first polypeptide comprising, from N-terminus to C-terminus, a first Fc region, the linker, and the sdAb; and a second polypeptide comprising a second Fc region. In some embodiments, the Fc fusion molecule comprises a first polypeptide comprising, from N-terminus to C-terminus, a first Fc region, the linker, and the sdAb; and a second polypeptide comprising a second Fc region, where the first Fc region and / or the second Fc region are modified.Fc Regions

[0256] In some embodiments, the Fc fusion molecule comprises a modified Fc region. In some embodiments, the Fc region (e.g., the first Fc region and / or the second Fc region) is modified to increase binding to FcRn at physiological pH. In some embodiments, the FcAttorney Docket No. VRD-024WO1 region is modified to increase binding to FcRn at pH between 6.8-7.8. In some embodiments, the Fc region is modified to increase binding to FcRn at pH between 7.0-7.4. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 6.8. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 6.9. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 7.0. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 7.1. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 7.2. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 7.3. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 7.4.

[0257] In some embodiments, the Fc region (e.g., the first Fc region and / or the second Fc region) is modified to increase binding to FcRn at endosomal pH. In some embodiments, the Fc region is modified to increase binding to FcRn at acidic pH. In some embodiments, the Fc region is modified to increase binding to FcRn at pH between 5.8-6.6. In some embodiments, the Fc region is modified to increase binding to FcRn at pH between 6.0-6.4. In some embodiments, the Fc region is modified to increase binding to FcRn at pH between 6.2-6.4. In some embodiments, the Fc region is modified to increase binding to FcRn at pH between 5.8-6.4. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 5.8. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 6.0. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 6.1. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 6.2. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 6.3. In some embodiments, the Fc region is modified to increase binding to FcRn at pH 6.4.

[0258] In some embodiments, the Fc region (e.g., the first Fc region and / or the second Fc region) is modified to increase binding to FcRn at both physiological and endosomal pH. In some embodiments, the Fc region is modified to increase binding to FcRn at both pH 7.4 and 6.0.

[0259] In some embodiments, the Fc region (e.g., the first Fc region and / or the second Fc region) is modified to promote heterodimerization. In some embodiments, the Fc region is modified to promote heterodimerization and to increase binding to FcRn at both physiological and endosomal pH. In some embodiments, the Fc region is modified to promote heterodimerization and to increase binding to FcRn at both pH 7.4 and 6.0.

[0260] In some embodiments, the Fc region (e.g., the first Fc region and / or the second Fc region) is derived from an IgGl, IgG2, IgG3, or IgG4 Fc region. In some embodiments, theAttorney Docket No. VRD-024WO1Fc region is derived from an IgGl Fc region. In some embodiments, the Fc region is derived from an IgG2 Fc region. In some embodiments, the Fc region is derived from an IgG3 Fc region. In some embodiments, the Fc region is derived from an IgG4 Fc region.

[0261] Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al, Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991.FcRn binding mutations

[0262] In some embodiments, the Fc fusion molecule comprises an Fc region (e.g., the first Fc region and / or the second Fc region) with one or more amino acid substitutions that increase binding to human neonatal Fc receptor (FcRn) as compared to the wild-type Fc region.

[0263] In some embodiments, the Fc region comprises one or more amino acid substitutions at position 237, 238, 239, 248, 250, 252, 253, 254, 255, 256, 257, 258, 265, 270, 272, 286, 288, 289, 297, 298, 303, 305, 307, 308, 309, 311, 312, 314, 315, 317, 325, 332, 334, 340, 356, 360, 362, 376, 378, 380, 382, 384, 385, 386, 387, 388, 389, 400, 413, 415, 424, 428, 433, 434, 435, 436, 439, or 447, wherein the positions are numbered according to the EU index.

[0264] In some embodiments, the Fc region comprises one or more amino acid substitutions selected from the group consisting of 237M, 238A, 239K, 2481, 250A, 250F, 2501, 250M, 250Q, 250S, 250V, 250W, 250Y, 252F, 252W, 252Y, 254T, 255E, 256D, 256E, 256Q, 257A, 257G, 2571, 257L, 257M, 257N, 257S, 257T, 257V, 258H, 265A, 270F, 286A, 286E, 289H, 297A, 298G, 303A, 305A, 307A, 307D, 307F, 307G, 307H, 3071, 307K, 307L, 307M, 307N, 307P, 307Q, 307R, 307S, 307V, 307W, 307Y, 308A, 308F, 3081, 308L, 308M, 308P, 308Q, 308T, 309A, 309D, 309E, 309P, 309R, 311A, 311H, 3111, 31 IK, 312A, 312H, 314K, 314R, 315A, 315H, 317A, 325G, 332V, 334L, 360H, 376A, 378V, 380A, 382A, 384A, 385D, 385H, 386P, 387E, 389A, 389S, 424A, 428 A, 428D, 428F, 428G, 428H, 4281, 428K, 428L, 428N, 428P, 428Q, 428S, 428T, 428V, 428W, 428Y, 433K, 433R, 434A, 434F, 434H, 434S, 434W, 434Y, 436H, 4361, and 436F, wherein the positions are numbered according to the EU index.

[0265] In some embodiments, the Fc region comprises one amino acid substitution. In some embodiments, the Fc region comprises two amino acid substitutions. In someAttorney Docket No. VRD-024WO1 embodiments, the Fc region comprises three amino acid substitutions. In some embodiments, the Fc region comprises four amino acid substitutions. In some embodiments, the Fc region comprises five amino acid substitutions. In some embodiments, the Fc region comprises six amino acid substitutions. In some embodiments, the Fc region comprises seven amino acid substitutions. In some embodiments, the Fc region comprises eight amino acid substitutions. In some embodiments, the Fc region comprises nine amino acid substitutions. In some embodiments, the Fc region comprises ten amino acid substitutions. In some embodiments, the Fc region comprises greater than ten amino acid substitutions.

[0266] In some embodiments, the Fc region comprises an amino acid substitution at position 237, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 237M.

[0267] In some embodiments, the Fc region comprises an amino acid substitution at position 238, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 238 A.

[0268] In some embodiments, the Fc region comprises an amino acid substitution at position 239, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 239K.

[0269] In some embodiments, the Fc region comprises an amino acid substitution at position 248, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 2481.

[0270] In some embodiments, the Fc region comprises an amino acid substitution at position 250, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 250A. In some embodiments, the Fc region comprises an amino acid substitution of 250F. In some embodiments, the Fc region comprises an amino acid substitution of 2501. In some embodiments, the Fc region comprises an amino acid substitution of 250M. In some embodiments, the Fc region comprises an amino acid substitution of 250Q. In some embodiments, the Fc region comprises an amino acid substitution of 250S. In some embodiments, the Fc region comprises an amino acid substitution of 250V. In some embodiments, the Fc region comprises an amino acid substitution of 250W. In some embodiments, the Fc region comprises an amino acid substitution of 250Y.

[0271] In some embodiments, the Fc region comprises an amino acid substitution at position 252, numbered according to the EU index. In some embodiments, the Fc regionAttorney Docket No. VRD-024WO1 comprises an amino acid substitution of 252F. In some embodiments, the Fc region comprises an amino acid substitution of 252W. In some embodiments, the Fc region comprises an amino acid substitution of 252Y.

[0272] In some embodiments, the Fc region comprises an amino acid substitution at position 253, numbered according to the EU index.

[0273] In some embodiments, the Fc region comprises an amino acid substitution at position 254, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 254T.

[0274] In some embodiments, the Fc region comprises an amino acid substitution at position 255, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 255E.

[0275] In some embodiments, the Fc region comprises an amino acid substitution at position 256, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 256D. In some embodiments, the Fc region comprises an amino acid substitution of 256E. In some embodiments, the Fc region comprises an amino acid substitution of 256Q.

[0276] In some embodiments, the Fc region comprises an amino acid substitution at position 257, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 257A. In some embodiments, the Fc region comprises an amino acid substitution of 257G. In some embodiments, the Fc region comprises an amino acid substitution of 2571. In some embodiments, the Fc region comprises an amino acid substitution of 257L. In some embodiments, the Fc region comprises an amino acid substitution of 257M. In some embodiments, the Fc region comprises an amino acid substitution of 257N. In some embodiments, the Fc region comprises an amino acid substitution of 257S. In some embodiments, the Fc region comprises an amino acid substitution of 257T. In some embodiments, the Fc region comprises an amino acid substitution of 257V.

[0277] In some embodiments, the Fc region comprises an amino acid substitution at position 258, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 258H.

[0278] In some embodiments, the Fc region comprises an amino acid substitution at position 265, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 265A.Attorney Docket No. VRD-024WO1

[0279] In some embodiments, the Fc region comprises an amino acid substitution at position 270, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 270F.

[0280] In some embodiments, the Fc region comprises an amino acid substitution at position 286, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 286A. In some embodiments, the Fc region comprises an amino acid substitution of 286E.

[0281] In some embodiments, the Fc region comprises an amino acid substitution at position 289, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 289H.

[0282] In some embodiments, the Fc region comprises an amino acid substitution at position 297, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 297A.

[0283] In some embodiments, the Fc region comprises an amino acid substitution at position 298, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 298G.

[0284] In some embodiments, the Fc region comprises an amino acid substitution at position 303, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 303 A.

[0285] In some embodiments, the Fc region comprises an amino acid substitution at position 305, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 305A.

[0286] In some embodiments, the Fc region comprises an amino acid substitution at position 307, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 307A. In some embodiments, the Fc region comprises an amino acid substitution of 307D. In some embodiments, the Fc region comprises an amino acid substitution of 307F. In some embodiments, the Fc region comprises an amino acid substitution of 307G. In some embodiments, the Fc region comprises an amino acid substitution of 307H. In some embodiments, the Fc region comprises an amino acid substitution of 3071. In some embodiments, the Fc region comprises an amino acid substitution of 307K. In some embodiments, the Fc region comprises an amino acid substitution of 307L. In some embodiments, the Fc region comprises an amino acid substitution of 307M. In some embodiments, the Fc region comprises an amino acidAttorney Docket No. VRD-024WO1 substitution of 307N. In some embodiments, the Fc region comprises an amino acid substitution of 307P. In some embodiments, the Fc region comprises an amino acid substitution of 307Q. In some embodiments, the Fc region comprises an amino acid substitution of 307R. In some embodiments, the Fc region comprises an amino acid substitution of 307S. In some embodiments, the Fc region comprises an amino acid substitution of 307V. In some embodiments, the Fc region comprises an amino acid substitution of 307W. In some embodiments, the Fc region comprises an amino acid substitution of 307Y.

[0287] In some embodiments, the Fc region comprises an amino acid substitution at position 308, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 308A. In some embodiments, the Fc region comprises an amino acid substitution of 308F. In some embodiments, the Fc region comprises an amino acid substitution of 3081. In some embodiments, the Fc region comprises an amino acid substitution of 308L. In some embodiments, the Fc region comprises an amino acid substitution of 308M. In some embodiments, the Fc region comprises an amino acid substitution of 308P. In some embodiments, the Fc region comprises an amino acid substitution of 308Q. In some embodiments, the Fc region comprises an amino acid substitution of 308T.

[0288] In some embodiments, the Fc region comprises an amino acid substitution at position 309, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 309A. In some embodiments, the Fc region comprises an amino acid substitution of 309D. In some embodiments, the Fc region comprises an amino acid substitution of 309E. In some embodiments, the Fc region comprises an amino acid substitution of 309P. In some embodiments, the Fc region comprises an amino acid substitution of 309R.

[0289] In some embodiments, the Fc region comprises an amino acid substitution at position 311, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 311 A. In some embodiments, the Fc region comprises an amino acid substitution of 311H. In some embodiments, the Fc region comprises an amino acid substitution of 31 II. In some embodiments, the Fc region comprises an amino acid substitution of 31 IK.

[0290] In some embodiments, the Fc region comprises an amino acid substitution at position 312, numbered according to the EU index. In some embodiments, the Fc regionAttorney Docket No. VRD-024WO1 comprises an amino acid substitution of 312A. In some embodiments, the Fc region comprises an amino acid substitution of 312H.

[0291] In some embodiments, the Fc region comprises an amino acid substitution at position 314, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 314K. In some embodiments, the Fc region comprises an amino acid substitution of 314R.

[0292] In some embodiments, the Fc region comprises an amino acid substitution at position 315, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 315A. n some embodiments, the Fc region comprises an amino acid substitution of 315H.

[0293] In some embodiments, the Fc region comprises an amino acid substitution at position 317, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 317A.

[0294] In some embodiments, the Fc region comprises an amino acid substitution at position 325, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 325G.

[0295] In some embodiments, the Fc region comprises an amino acid substitution at position 332, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 332V.

[0296] In some embodiments, the Fc region comprises an amino acid substitution at position 334, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 334L.

[0297] In some embodiments, the Fc region comprises an amino acid substitution at position 360, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 360H.

[0298] In some embodiments, the Fc region comprises an amino acid substitution at position 376, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 376A.

[0299] In some embodiments, the Fc region comprises an amino acid substitution at position 378, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 378V.Attorney Docket No. VRD-024WO1

[0300] In some embodiments, the Fc region comprises an amino acid substitution at position 380, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 380A.

[0301] In some embodiments, the Fc region comprises an amino acid substitution at position 382, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 382A.

[0302] In some embodiments, the Fc region comprises an amino acid substitution at position 384, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 384A.

[0303] In some embodiments, the Fc region comprises an amino acid substitution at position 385, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 385D. In some embodiments, the Fc region comprises an amino acid substitution of 385H.

[0304] In some embodiments, the Fc region comprises an amino acid substitution at position 386, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 386P.

[0305] In some embodiments, the Fc region comprises an amino acid substitution at position 387 numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 387E.

[0306] In some embodiments, the Fc region comprises an amino acid substitution at position 389, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 389A. In some embodiments, the Fc region comprises an amino acid substitution of 389S.

[0307] In some embodiments, the Fc region comprises an amino acid substitution at position 424, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 424A.

[0308] In some embodiments, the Fc region comprises an amino acid substitution at position 428, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 428A. In some embodiments, the Fc region comprises an amino acid substitution of 428D. In some embodiments, the Fc region comprises an amino acid substitution of 428F. In some embodiments, the Fc region comprises an amino acid substitution of 428G. In some embodiments, the Fc region comprises an amino acid substitution of 428H. In some embodiments, the Fc regionAttorney Docket No. VRD-024WO1 comprises an amino acid substitution of 4281. In some embodiments, the Fc region comprises an amino acid substitution of 428K. In some embodiments, the Fc region comprises an amino acid substitution of 428L. In some embodiments, the Fc region comprises an amino acid substitution of 428N. In some embodiments, the Fc region comprises an amino acid substitution of 428P. In some embodiments, the Fc region comprises an amino acid substitution of 428Q. In some embodiments, the Fc region comprises an amino acid substitution of 428S. In some embodiments, the Fc region comprises an amino acid substitution of 428T. In some embodiments, the Fc region comprises an amino acid substitution of 428V. In some embodiments, the Fc region comprises an amino acid substitution of 428W. In some embodiments, the Fc region comprises an amino acid substitution of 428Y.

[0309] In some embodiments, the Fc region comprises an amino acid substitution at position 433, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 433K. In some embodiments, the Fc region comprises an amino acid substitution of 433R.

[0310] In some embodiments, the Fc region comprises an amino acid substitution at position 434, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 434A. In some embodiments, the Fc region comprises an amino acid substitution of 434F. In some embodiments, the Fc region comprises an amino acid substitution of 434H. In some embodiments, the Fc region comprises an amino acid substitution of 434S. In some embodiments, the Fc region comprises an amino acid substitution of 434W. In some embodiments, the Fc region comprises an amino acid substitution of 434Y.

[0311] In some embodiments, the Fc region comprises an amino acid substitution at position 436, numbered according to the EU index. In some embodiments, the Fc region comprises an amino acid substitution of 436H. In some embodiments, the Fc region comprises an amino acid substitution of 4361. In some embodiments, the Fc region comprises an amino acid substitution of 436F.

[0312] In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and 434, wherein the positions are numbered according to the EU index.Attorney Docket No. VRD-024WO1

[0313] In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 433, and / or 434, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 433, and 434, wherein the positions are numbered according to the EU index.

[0314] In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 428, 433, and / or 434, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 428, 433, and 434, wherein the positions are numbered according to the EU index.

[0315] In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 428, and / or 434, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions at positions 252, 254, 256, 428, and 434, wherein the positions are numbered according to the EU index.

[0316] In some embodiments the Fc region comprises amino acid substitutions (i) 434Y and (ii) 433R or 433K, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region further comprises amino acid substitutions of 252Y, 254T, and 256E. In some embodiments, the Fc region further comprises the amino acid substitution of 428L.

[0317] In some embodiments the Fc region comprises amino acid substitutions 434Y and 433R, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region further comprises amino acid substitutions of 252Y, 254T, and 256E. In some embodiments, the Fc region further comprises the amino acid substitution of 428L.

[0318] In some embodiments the Fc region comprises amino acid substitutions 434Y and 433K, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region further comprises amino acid substitutions of 252Y, 254T, and 256E. In some embodiments, the Fc region further comprises the amino acid substitution of 428L.

[0319] In some embodiments, the Fc region comprises amino acid substitutions of 428L and 434F, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region further comprises amino acid substitutions of 252Y, 254T, and 256E. In some embodiments, the Fc region further comprises the amino acid substitution of 433R or 433K.Attorney Docket No. VRD-024WO1

[0320] In some embodiments, the Fc region comprises amino acid substitutions of 433R and 434F, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region further comprises amino acid substitutions of 252Y, 254T, and 256E. In some embodiments, the Fc region further comprises the amino acid substitution of 428L.

[0321] In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and / or 434F, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434F, wherein the positions are numbered according to the EU index.

[0322] In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and / or 434Y, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, wherein the positions are numbered according to the EU index.

[0323] In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433R, and / or 434Y, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433R, and 434Y, wherein the positions are numbered according to the EU index.

[0324] In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433R, and / or 434F, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433R, and 434F, wherein the positions are numbered according to the EU index.

[0325] In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and / or 434F, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, wherein the positions are numbered according to the EU index.

[0326] In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and / or 434Y, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434Y, wherein the positions are numbered according to the EU index.Attorney Docket No. VRD-024WO1

[0327] In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433R, and / or 434F, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433R, and 434F, wherein the positions are numbered according to the EU index.

[0328] In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, and / or 434F, wherein the positions are numbered according to the EU index. In some embodiments, the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, and 434F, wherein the positions are numbered according to the EU index.Other Fc Modifications

[0329] In some embodiments, the Fc region (e.g., the first Fc region and / or the second Fc region) is further modified to promote heterodimerization. In some embodiments, the Fc region is modified using knob-in-to-hole mutations. In some embodiments, the Fc region is modified using strand-exchange engineered domain (SEED). In some embodiments, the Fc region is modified using steric modification technology.

[0330] In some embodiments, the Fc region is modified using knob-in-to-hole mutations to promote Fc dimerization. In some embodiments, the Fc region comprises one or more amino acid substitutions selected from the group consisting of Y349C, S354C, T366S, T366W, T366Y L368A, Y407V, and Y407T. In some embodiments, a first Fc region is modified with “hole” mutations and a second Fc region is modified with “knob” mutations.

[0331] In some embodiments, the “hole” mutations comprise the amino acid substitutions of Y349C, T366S, L368A, and Y407V, and the “knob” mutations comprise S354C and T366W. In some embodiments, the “hole” mutations comprise T366S, L368A, and Y407V, and the “knob” mutations comprise T366W.

[0332] In some embodiments, the Fc region comprises knob-in-to-hole mutations in addition to one or more amino acid substitutions that increase binding to human neonatal Fc receptor (FcRn) as compared to the wild-type Fc region.Exemplary Fc Regions

[0333] In some embodiments, the Fc region (e.g., the first Fc region and / or the second Fc region) comprises an amino acid sequence selected from Table A. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to an amino acid sequence selected from Table A. In some embodiments, the Fc region comprises an amino acidAttorney Docket No. VRD-024WO1 sequence at least 70% identical to an amino acid sequence selected from Table A. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to an amino acid sequence selected from Table A. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to an amino acid sequence selected from Table A. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to an amino acid sequence selected from Table A. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to an amino acid sequence selected from Table A. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to an amino acid sequence selected from Table A. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to an amino acid sequence selected from Table A. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to an amino acid sequence selected from Table A. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to an amino acid sequence selected from Table A.Table A. Amino Acid Sequences of Exemplary Fc RegionsAttorney Docket No. VRD-024WO1Attorney Docket No. VRD-024WO1Attorney Docket No. VRD-024WO1Attorney Docket No. VRD-024WO1

[0334] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 12-38. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to any one of SEQ ID NOs: 12-38. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to any one of SEQ ID NOs: 12-38. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to any one of SEQ ID NOs: 12-38. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 12-38. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 12-38. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 12-38. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 12-38. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 12-38. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 12-38. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 12-38. In some embodiments, the Fc region comprises an amino acid sequence identical to any one of SEQ ID NOs: 12-38.

[0335] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 12. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 12. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 12. In some embodiments, the FcAttorney Docket No. VRD-024WO1 region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 12. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 12. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 12. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 12. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 12. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 12. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 12. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 12.

[0336] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 13. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 13. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 13. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 13. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 13. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 13. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 13. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 13. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 13. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 13. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 13.

[0337] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 14. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 14. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 14. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 14. In someAttorney Docket No. VRD-024WO1 embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 14. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 14. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 14. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 14. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 14. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 14. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 14.

[0338] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 15. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 15.

[0339] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 16. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 16. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 16. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 16. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQAttorney Docket No. VRD-024WO1ID NO: 16. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 16. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 16. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 16. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 16. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 16. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 16.

[0340] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 17. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 17. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 17. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 17. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 17. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 17. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 17. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 17. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 17. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 17. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 17. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 17.

[0341] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at leastAttorney Docket No. VRD-024WO195% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 18.

[0342] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 19. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 19.

[0343] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 20. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 20. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 20. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 20. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 20. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 20. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 20. In some embodiments, the Fc region comprises an aminoAttorney Docket No. VRD-024WO1 acid sequence at least 96% identical to SEQ ID NO: 20. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 20. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 20. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 20. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 20.

[0344] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 21. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 21. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 21. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 21. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 21. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 21. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 21. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 21. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 21. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 21. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 21. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 21.

[0345] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 22. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 22. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 22. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 22. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 22. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 22. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 22. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 22. In some embodiments, the Fc regionAttorney Docket No. VRD-024WO1 comprises an amino acid sequence at least 97% identical to SEQ ID NO: 22. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 22. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 22. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 22.

[0346] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 23. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 23. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 23. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 23. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 23. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 23. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 23. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 23. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 23. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 23. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 23.

[0347] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 24. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 24. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 24. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 24. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 24. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 24. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 24. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 24. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 24. In someAttorney Docket No. VRD-024WO1 embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 24. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 24. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 24.

[0348] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 25. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 25. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 25. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 25. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 25. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 25. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 25. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 25. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 25. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 25. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 25. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 25.

[0349] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 26 In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 26. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 26. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 26. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 26. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 26. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 26. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 26. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQAttorney Docket No. VRD-024WO1ID NO: 26. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 26. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 26.

[0350] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 27. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 27. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 27. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 27. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 27. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 27. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 27. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 27. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 27. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 27. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 27. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 27.

[0351] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 28. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 28. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 28. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 28. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 28. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 28. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 28. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 28. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 28. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 28. In some embodiments, the Fc region comprises an amino acid sequence at leastAttorney Docket No. VRD-024WO199% identical to SEQ ID NO: 28. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 28.

[0352] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 20. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 29. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 29. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 29. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 29. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 29. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 29. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 29. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 29. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 29. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 29. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 29.

[0353] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 30. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 30. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 30. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 30. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 30. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 30. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 30. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 30. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 30. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 30. In some embodiments, the Fc region comprises an amino acid sequence at leastAttorney Docket No. VRD-024WO199% identical to SEQ ID NO: 30. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 30.

[0354] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 31. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 31. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 31. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 31. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 31. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 31. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 31. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 31. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 31. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 31. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 31. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 31.

[0355] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 32. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 32. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 32. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 32. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 32. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 32. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 32. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 32. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 32. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 32. In some embodiments, the Fc region comprises an amino acid sequence at leastAttorney Docket No. VRD-024WO199% identical to SEQ ID NO: 32. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 32.

[0356] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 33. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 33. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 33. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 33. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 33. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 33. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 33. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 33. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 33. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 33. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 33. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 33.

[0357] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence at leastAttorney Docket No. VRD-024WO199% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 34.

[0358] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 35. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 35. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 35. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 35. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 35. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 35. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 35. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 35. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 35. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 35. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 35. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 35.

[0359] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 36. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 36. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 36. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 36. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 36. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 36. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 36. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 36. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 36. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 36. In some embodiments, the Fc region comprises an amino acid sequence at leastAttorney Docket No. VRD-024WO199% identical to SEQ ID NO: 36. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 36.

[0360] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 37. In some embodiments, the Fc region comprises an amino acid sequence identical to SEQ ID NO: 37.

[0361] In some embodiments, the Fc region comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 38. In some embodiments, the Fc region comprises an amino acid sequence at least 60% identical to SEQ ID NO: 38. In some embodiments, the Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 38. In some embodiments, the Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 38. In some embodiments, the Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 38. In some embodiments, the Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 38. In some embodiments, the Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 38. In some embodiments, the Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 38. In some embodiments, the Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 38. In some embodiments, the Fc region comprises an amino acid sequence at least 98% identical to SEQ ...

Claims

Attorney Docket No. VRD-024WO1CLAIMS1. A method of treating an immunoglobulin G (IgG)-mediated disease or disorder comprising subcutaneously administering an Fc fusion molecule that binds neonatal Fc receptor (FcRn) at a dose of between 300 mg to 3000 mg, wherein the Fc fusion molecule comprises from N-terminus to C-terminus or C- terminus to N-terminus: a) an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; b) a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and c) a sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

2. A method for reducing an IgG level in a subject comprising subcutaneously administering an Fc fusion molecule that binds neonatal Fc receptor (FcRn) at a dose of between 300 mg to 3000 mg, wherein the Fc fusion molecule comprises from N-terminus to C-terminus or C- terminus to N-terminus: a) an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; b) a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and c) a sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

3. The method of claim 1 or 2, wherein the Fc fusion molecule is administered at a dose of 300 mg to 2400 mg, 300 mg to 1200 mg, 300 mg to 600 mg, 600 mg to 3000 mg, 600 mg to 2400 mg, 600 mg to 1200 mg, 1200 mg to 3000 mg, 1200 mg to 2400 mg, or 2400 mg to 3000 mg.Attorney Docket No. VRD-024WO14. The method of any one of claims 1-3, wherein the dose is 300 mg, 600 mg, 1200 mg, 2400 mg, or 3000 mg.

5. The method of any one of the preceding claims, wherein the Fc fusion molecule is administered with a syringe pump delivery system.

6. The method of claim 5, wherein the syringe pump delivery system is an on-body device.

7. The method of any one of the preceding claims, wherein the Fc fusion molecule dose is administered at an infusion rate of 0.5 mL / min to 2.0 mL / min.

8. The method of claim 7, wherein the Fc fragment dose is administered at an infusion rate of 0.8 mL / min.

9. The method of any one of the preceding claims, wherein the Fc fusion molecule dose is administered in 2 min to 30 min.

10. The method of any one of the preceding claims, wherein the Fc fusion molecule is administered without co-administration of hyaluronidase.

11. The method of any one of the preceding claims, wherein the Fc fusion molecule is administered no more frequently than once every week.

12. The method of any one of the preceding claims, wherein the Fc fusion molecule is administered once every week, once every two weeks, once every three weeks, once every four weeks, or once every eight weeks.

13. A method of treating an IgG-mediated disease or disorder comprising intravenously administering an Fc fusion molecule that binds neonatal Fc receptor (FcRn) at a dose of between 1 mg / kg to 50 mg / kg, wherein the Fc fusion molecule comprises from N-terminus to C-terminus or C- terminus to N-terminus: a) an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index;Attorney Docket No. VRD-024WO1 b) a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and c) a sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

14. A method for reducing an IgG level in a subject comprising intravenously administering an Fc fusion molecule that binds neonatal Fc receptor (FcRn) at a dose of between 1 mg / kg to 50 mg / kg, wherein the Fc fusion molecule comprises from N-terminus to C-terminus or C- terminus to N-terminus: a) an Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; b) a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and c) a sdAb that binds to HSA comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101).

15. The method of claim 13 or 14, wherein the Fc fusion molecule is administered at a dose of 1 mg / kg to 6 mg / kg, 3 mg / kg to 7 mg / kg, 4 mg / kg to 10 mg / kg, 5 mg / kg to 11 mg / kg, 6 mg / kg to 12 mg / kg, 7 mg / kg to 13 mg / kg, 8 mg / kg to 14 mg / kg, 9 mg / kg to 15 mg / kg, 10 mg / kg to 16 mg / kg, 11 mg / kg to 17 mg / kg, 12 mg / kg to 18 mg / kg, 13 mg / kg to 19 mg / kg, 14 mg / kg to 20 mg / kg, 10 mg / kg to 20 mg / kg, 15 mg / kg to 20 mg / kg, 20 mg / kg to 30 mg / kg, 25 mg / kg to 30 mg / kg, 25 mg / kg to 35 mg / kg, 30 mg / kg to 35 mg / kg, 30 mg / kg to 40 mg / kg, 35 mg / kg to 40 mg / kg, 40 mg / kg to 50 mg / kg, or 45 mg / kg to 50 mg / kg.

16. The method of any one of claims 13-15, wherein the Fc fusion molecule is administered at a dose of 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, 24 mg / kg, 25Attorney Docket No. VRD-024WO1 mg / kg, 26 mg / kg, 27 mg / kg, 28 mg / kg, 29 mg / kg, 30 mg / kg, 31 mg / kg, 32 mg / kg, 33 mg / kg, 34 mg / kg, 35 mg / kg, 36 mg / kg, 37 mg / kg, 38 mg / kg, 39 mg / kg, 40 mg / kg, 41 mg / kg, 42 mg / kg, 43 mg / kg, 44 mg / kg, 45 mg / kg, 46 mg / kg, 47 mg / kg, 48 mg / kg, 49 mg / kg, or 50 mg / kg.

17. The method of any one of claims 13-16, wherein the Fc fusion molecule dose is administered at an infusion rate of 4.2 mL / min.

18. The method of any one of the preceding claims, wherein the Fc fusion molecule is administered in a single dose.

19. The method of any one of the preceding claims, wherein administering the Fc fusion molecule reduces the IgG level to less than 90%, to less than 85%, to less than 80%, to less than 75%, to less than 70%, to less than 65%, to less than 60%, to less than 55%, to less than 50% as compared to an IgG level prior to the administration of the Fc fusion molecule.

20. The method of any one of the preceding claims, wherein administering the Fc fusion molecule region reduces the IgG level for more than 10 days, more than 15 days, more than 20 days, more than 25 days, or more than 30 days as compared to an IgG level prior to administration of the Fc fusion molecule.

21. The method of any one of claims 1-20, wherein the Fc region comprises a lysine residue at a C-terminus.

22. The method of any one of claims 1-21, wherein the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1.

23. The method of any one of claims 1-22, wherein the sdAb comprises an amino acid sequence identical to SEQ ID NO: 1.

24. The method of any one of claims 1-23, wherein the Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37.

25. The method of claim 24, wherein the Fc region comprises an amino acid sequence identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37.Attorney Docket No. VRD-024WO126. The method of any one of the preceding claims, wherein the linker comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 repeating units of GGGGS (SEQ ID NO: 181).

27. The method of any one of the preceding claims, wherein the linker comprises 6 repeating units of GGGGS (SEQ ID NO: 181).

28. The method of any one of claims 1-27, wherein the linker comprises 8 repeating units of GGGGS (SEQ ID NO: 181).

29. The method of any one of claims 1-28, wherein the Fc fusion molecule comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 55.

30. The method of any one of claims 1-29, wherein the Fc fusion molecule comprises an amino acid sequence of SEQ ID NO: 55.

31. The method of any one of the preceding claims, wherein the Fc fusion molecule forms a heterodimer.

32. The method of any one of claims 1-30, wherein the Fc fusion molecule forms a homodimer.

33. The method of any one of claims 1-31, wherein the Fc fusion molecule comprises a first polypeptide comprising, from N-terminus to C-terminus, a first Fc region, the linker, and the sdAb; and a second polypeptide comprising a second Fc region.

34. The method of claim 33, wherein the first Fc region and the second Fc region comprise the same amino acid substitutions.

35. The method of claim 33, wherein the first Fc region and the second Fc region comprise different amino acid substitutions.

36. The method of any one of claims 33-35, wherein the first Fc region further comprises amino acid substitutions T366S, L368A, and Y407V, and the second Fc region further comprises amino acid substitution T366W.Attorney Docket No. VRD-024WO137. The method of any one of claims 33-35, wherein the second Fc region further comprises amino acid substitutions T366S, L368A, and Y407V, and the first Fc region further comprises amino acid substitution T366W.

38. The method of any one of claims 33-35, wherein the first Fc region further comprises amino acid substitutions Y349C, T366S, L368A, and Y407V, and the second Fc region further comprises amino acid substitutions S354C and T366W.

39. The method of any one of claims 33-35, wherein the second Fc region further comprises amino acid substitutions Y349C, T366S, L368A, and Y407V, and the first Fc region further comprises amino acid substitutions S354C and T366W.

40. The method of any one of claims 1-39, wherein the first polypeptide comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 19.

41. The method of claim 40, wherein the first polypeptide comprises an amino acid sequence of SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence of SEQ ID NO: 19.

42. The method of any one of claims 1-41, wherein the Fc fusion molecule is coadministered with hyaluronidase.

43. A method of treating an IgG-mediated disease or disorder comprising subcutaneously administering a molecule that binds neonatal Fc receptor (FcRn) at a dose of between 300 mg to 3000 mg, wherein the molecule comprises a first polypeptide comprising from N-terminus to C-terminus or C-terminus to N- terminus: a. a first Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; b. a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and c. a sdAb comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence ofAttorney Docket No. VRD-024WO1AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index.

44. A method for reducing an IgG level in a subject comprising subcutaneously administering a molecule that binds neonatal Fc receptor (FcRn) at a dose of between 300 mg to 3000 mg, wherein the molecule comprises a first polypeptide comprising from N-terminus to C-terminus or C-terminus to N- terminus: a. a first Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; b. a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and c. a sdAb comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index.

45. The method of claim 43 or 44, wherein the molecule is administered at a dose of 300 mg to 2400 mg, 300 mg to 1200 mg, 300 mg to 600 mg, 600 mg to 3000 mg, 600 mg to 2400 mg, 600 mg to 1200 mg, 1200 mg to 3000 mg, 1200 mg to 2400 mg, or 2400 mg to 3000 mg.

46. The method of any one of claims 43-45, wherein the dose is 300 mg, 600 mg, 1200 mg, 2400 mg, or 3000 mg.

47. The method of any one of claims 43-46, wherein the molecule is administered with a syringe pump delivery system.Attorney Docket No. VRD-024WO148. The method of claim 47, wherein the syringe pump delivery system is an on-body device.

49. The method of any one of claims 43-48, wherein the molecule dose is administered at an infusion rate of 0.5 mL / min to 2.0 mL / min.

50. The method of claim 49, wherein the molecule dose is administered at an infusion rate of 0.8 mL / min.

51. The method of any one of claims 43-50, wherein the molecule dose is administered in 2 min to 30 min.

52. The method of any one of claims 43-51, wherein the molecule is administered without co-administration of hyaluronidase.

53. The method of any one of claims 43-52, wherein the molecule is administered no more frequently than once every week.

54. The method of any one of claims 43-53, wherein the molecule is administered once every week, once every two weeks, once every three weeks, once every four weeks, or once every eight weeks.

55. A method of treating an IgG-mediated disease or disorder comprising intravenously administering a molecule that binds neonatal Fc receptor (FcRn) at a dose of between 1 mg / kg to 50 mg / kg, wherein the molecule comprises a first polypeptide comprising from N-terminus to C-terminus or C-terminus to N- terminus: a. a first Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; b. a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and c. a sdAb comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101); andAttorney Docket No. VRD-024WO1 a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index.

56. A method for reducing an IgG level in a subject comprising intravenously administering a molecule that binds neonatal Fc receptor (FcRn) at a dose of between 1 mg / kg to 50 mg / kg, wherein the molecule comprises a first polypeptide comprising from N-terminus to C-terminus or C-terminus to N- terminus: a. a first Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index; b. a linker comprising one or more repeating units of GGGGS (SEQ ID NO: 181); and c. a sdAb comprising a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 comprising an amino acid sequence of GQSTSR (SEQ ID NO: 101); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, numbered according to the EU index.

57. The method of claim 55 or 56, wherein the molecule is administered at a dose of 1 mg / kg to 6 mg / kg, 3 mg / kg to 7 mg / kg, 4 mg / kg to 10 mg / kg, 5 mg / kg to 11 mg / kg, 6 mg / kg to 12 mg / kg, 7 mg / kg to 13 mg / kg, 8 mg / kg to 14 mg / kg, 9 mg / kg to 15 mg / kg, 10 mg / kg to 16 mg / kg, 11 mg / kg to 17 mg / kg, 12 mg / kg to 18 mg / kg, 13 mg / kg to 19 mg / kg, 14 mg / kg to20 mg / kg, 10 mg / kg to 20 mg / kg, 15 mg / kg to 20 mg / kg, 20 mg / kg to 30 mg / kg, 25 mg / kg to30 mg / kg, 25 mg / kg to 35 mg / kg, 30 mg / kg to 35 mg / kg, 30 mg / kg to 40 mg / kg, 35 mg / kg to40 mg / kg, 40 mg / kg to 50 mg / kg, or 45 mg / kg to 50 mg / kg.

58. The method of any one of claims 55-57, wherein the molecule is administered at a dose of 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg 11 mg / kg, 12 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, 24 mg / kg, 25 mg / kg, 26 mg / kg, 27 mg / kg, 28 mg / kg, 29 mg / kg, 30 mg / kg, 31 mg / kg, 32 mg / kg, 33 mg / kg, 34 mg / kg, 35Attorney Docket No. VRD-024WO1 mg / kg, 36 mg / kg, 37 mg / kg, 38 mg / kg, 39 mg / kg, 40 mg / kg, 41 mg / kg, 42 mg / kg, 43 mg / kg, 44 mg / kg, 45 mg / kg, 46 mg / kg, 47 mg / kg, 48 mg / kg, 49 mg / kg, or 50 mg / kg.

59. The method of any one of claims 55-58, wherein the molecule dose is administered at an infusion rate of 4.2 mL / min.

60. The method of any one of claims 55-59, wherein the molecule is administered in a single dose.

61. The method of any one of claims 43-60, wherein administering the molecule reduces the IgG level to less than 90%, to less than 85%, to less than 80%, to less than 75%, to less than 70%, to less than 65%, to less than 60%, to less than 55%, to less than 50% as compared to an IgG level prior to the administration of the Fc fusion molecule.

62. The method of any one of claims 43-61, wherein administering the molecule region reduces the IgG level for more than 10 days, more than 15 days, more than 20 days, more than 25 days, or more than 30 days as compared to an IgG level prior to administration of the Fc fusion molecule.

63. The method of any one of claims 43-62, wherein the first Fc region and / or the second Fc region comprises a lysine residue at a C-terminus.

64. The method of any one of claims 43-63, wherein the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1.

65. The method of any one of claims 43-64, wherein the sdAb comprises an amino acid sequence identical to SEQ ID NO: 1.

66. The method of any one of claims 43-65, wherein the first Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37 and the second Fc region comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37.Attorney Docket No. VRD-024WO167. The method of claim 66, wherein the first Fc region comprises an amino acid sequence identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37 and the second Fc region comprises an amino acid sequence identical to any one of SEQ ID NOs: 15, 18-19, 34, or 37.

68. The method of any one of claims 43-67, wherein the linker comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 repeating units of GGGGS (SEQ ID NO: 181).

69. The method of any one of claims 43-68, wherein the linker comprises 6 repeating units of GGGGS (SEQ ID NO: 181).

70. The method of any one of claims 43-68, wherein the linker comprises 8 repeating units of GGGGS (SEQ ID NO: 181).

71. The method of any one of claims 43-70, wherein the first Fc region further comprises amino acid substitutions T366S, L368A, and Y407V, and the second Fc region further comprises amino acid substitution T366W.

72. The method of any one of claims 43-70, wherein the second Fc region further comprises amino acid substitutions T366S, L368A, and Y407V, and the first Fc region further comprises amino acid substitution T366W.

73. The method of any one of claims 43-70, wherein the first Fc region further comprises amino acid substitutions Y349C, T366S, L368A, and Y407V, and the second Fc region further comprises amino acid substitutions S354C and T366W.

74. The method of any one of claims 43-70, wherein the second Fc region further comprises amino acid substitutions Y349C, T366S, L368A, and Y407V, and the first Fc region further comprises amino acid substitutions S354C and T366W.

75. The method of any one of claims 43-74, wherein the first polypeptide comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 19.Attorney Docket No. VRD-024WO176. The method of claim 75, wherein the first polypeptide comprises an amino acid sequence of SEQ ID NO: 55, and the second polypeptide comprises an amino acid sequence of SEQ ID NO: 19.

77. The method of any one of claims 43-76, wherein the molecule is co-administered with hyaluronidase.

78. The method of any one of claims 1-42, wherein the half-life of the Fc fusion molecule is longer than the half-life of efgartigimod.

79. The method of any one of claims 43-77, wherein the half-life of the molecule is longer than the half-life of efgartigimod.

80. The method of any one of claims 1, 3-13, 15-43, 45-55, or 57-79, wherein the disease or disorder is an autoimmune disease, inflammatory disorder, or an ocular disorder.

81. The method of claim 1, 3-13, 15-43, 45-55, or 57-80, wherein the disease or disorder is generalized myasthenia gravis (gMG), Grave's disease, chronic inflammatory demyelinating polyneuropathy, myositis, autoimmune encephalitis, myelin oligodendrocyte glycoprotein antibody disorders (MOG-antibody disorder), membranous nephropathy, lupus nephritis, thyroid eye disease, warm autoimmune hemolytic anemia, hemolytic disease of the fetus and newborn, idiopathic inflammatory myopathy, idiopathic thrombocytopenic purpura, primary Sjogren’s Syndrome, systemic lupus erythematosus, rheumatoid arthritis, bullous pemphigoid, pemphigus foliaceus, pemphigus vulgaris, or cutaneous lupus erythematosus, antibody mediated rejection, systemic sclerosis, lupus neuropathy, or ocular myasthenia gravis.

82. The method of any one of the claims 1, 3-13, 15-43, 45-55, or 57-81, wherein the disease or disorder is associated with elevated levels of an IgG.

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