Anti-HSA antibody fusions and methods of use thereof

Abstract

The present disclosure provides, among other things, fusion proteins comprising an Fc region and a single domain antibody (sdAb) that binds to human serum albumin. Pharmaceutical compositions comprising the single domain antibodies disclosed herein and methods of using the same are provided.

Description

ATTORNEY DOCKET NO. VRD-021BWO1ANTI-HSA ANTIBODY FUSIONS AND METHODS OF USE THEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to, and the benefit of, U.S. Provisional Application No. 63 / 702,592, filed October 2, 2024, and U.S. Provisional Application No. 63 / 719,077, filed November 11, 2024, the disclosure of each of which is hereby incorporated by reference in its entirety.BACKGROUND

[0002] 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.SUMMARY OF THE INVENTION

[0003] The present disclosure provides, among other things, fusion proteins comprising an Fc region fused to a single domain antibody (sdAb) that binds to human serum albumin (HSA). Such fusion proteins comprising the anti-HSA sdAbs and therapeutic uses of such fusion proteins are effective in treating IgG autoantibody-mediated disease. As described herein, the present invention is, in part, based on the discovery that the anti-HSA sdAbs described herein, when fused to a therapeutic protein such as an Fc region that binds to FcRn, can significantly improve both the durability of the therapeutic protein and its magnitude of effect without affecting serum albumin levels. This is particularly important as low albumin levels can increase the risk of cardiovascular disease and drug toxicity. Thus, the disclosure provides Fc fusions comprising anti-HSA sdAbs, which anti-HSA sdAbs can increase therapeutic potential of fusion partners without harmful side effects. Moreover, these anti- HSA sdAbs described herein exhibit desirable characteristics that facilitate high yield production, cost-efficient purification, and improved stability.

[0004] In one aspect, the disclosure provides, among other things, fusion proteins comprising an Fc region fused to a single domain antibody (sdAb) that binds to human serum albumin (HSA).ATTORNEY DOCKET NO. VRD-021BWO1

[0005] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a single domain antibody (sdAb) that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 consisting of an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 consisting of an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0006] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 consisting of an amino acid sequence of AIDSGGADTRYAESVKG (SEQ ID NO: 96), and a CDR3 consisting of an amino acid sequence of GRSASR (SEQ ID NO: 102).

[0007] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of QFGMSATTORNEY DOCKET NO. VRD-021BWO1(SEQ ID NO: 92), a CDR2 consisting of an amino acid sequence of AISSDGSGTIYADSVKG (SEQ ID NO: 97), and a CDR3 consisting of an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0008] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of QFGMS (SEQ ID NO: 92), a CDR2 consisting of an amino acid sequence of AISSDASGTIYADSVKG (SEQ ID NO: 98), and a CDR3 consisting of an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0009] In one aspect, the present invention provides, among other things, a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of QFGMS (SEQ ID NO: 92), a CDR2 consisting of an amino acid sequence of AISSDSSGTIYADSVKG (SEQ ID NO: 99), and a CDR3 consisting of an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0010] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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:ATTORNEY DOCKET NO. VRD-021BWO1100), and a CDR3 comprising an amino acid sequence of GRSTSR (SEQ ID NO: 104). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 consisting of an amino acid sequence of AIDSGGADTRYAETVKG (SEQ ID NO: 100), and a CDR3 consisting of an amino acid sequence of GRSTSR (SEQ ID NO: 104).[OH] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of SAGMS (SEQ ID NO: 93), a CDR2 consisting of an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 consisting of an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0012] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of SFGAS (SEQ ID NO: 94), a CDR2 consisting of an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 consisting of an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0013] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434;ATTORNEY DOCKET NO. VRD-021BWO1 wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 consisting of an amino acid sequence of AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 consisting of an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0014] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein the sdAb comprises a CDR1 comprising an amino acid sequence of AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence of AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence of TIGRSASR (SEQ ID NO: 116). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 consisting of an amino acid sequence of AIDSGGADTR (SEQ ID NO: 111), and a CDR3 consisting of an amino acid sequence of TIGRSASR (SEQ ID NO: 116).

[0015] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 consisting of an amino acid sequence of AISSDGSGTI (SEQ ID NO: 112), and a CDR3 consisting of an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).ATTORNEY DOCKET NO. VRD-021BWO1

[0016] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 consisting of an amino acid sequence of AISSDASGTI (SEQ ID NO: 113), and a CDR3 consisting of an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0017] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 consisting of an amino acid sequence of AISSDSSGTI (SEQ ID NO: 114), and a CDR3 consisting of an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0018] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence ofATTORNEY DOCKET NO. VRD-021BWO1AASGFSFGSFGMS (SEQ ID NO: 107), a CDR2 consisting of an amino acid sequence of AIDSGGADTR (SEQ ID NO: 111), and a CDR3 consisting of an amino acid sequence of TIGRSTSR (SEQ ID NO: 118).

[0019] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGSAGMS (SEQ ID NO: 108), a CDR2 consisting of an amino acid sequence of AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 consisting of an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0020] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGSFGAS (SEQ ID NO: 109), a CDR2 consisting of an amino acid sequence of AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 consisting of an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0021] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGSFG (SEQ ID NO: 119), aATTORNEY DOCKET NO. VRD-021BWO1CDR2 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGSFG (SEQ ID NO: 119), a CDR2 consisting of an amino acid sequence of IDSGGTDT (SEQ ID NO: 123), and a CDR3 consisting of an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0022] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGSFG (SEQ ID NO: 119), a CDR2 consisting of an amino acid sequence of IDSGGADT (SEQ ID NO: 124), and a CDR3 consisting of an amino acid sequence of TIGRSASR (SEQ ID NO: 116).

[0023] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGQFG (SEQ ID NO: 120), a CDR2 consisting of an amino acid sequence of ISSDGSGT (SEQ ID NO: 125), and a CDR3 consisting of an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0024] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254,ATTORNEY DOCKET NO. VRD-021BWO1256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGQFG (SEQ ID NO: 120), a CDR2 consisting of an amino acid sequence of ISSDASGT (SEQ ID NO: 126), and a CDR3 consisting of an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0025] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGQFG (SEQ ID NO: 120), a CDR2 consisting of an amino acid sequence of ISSDSSGT (SEQ ID NO: 127), and a CDR3 consisting of an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0026] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFSFGSFG (SEQ ID NO: 121), a CDR2 consisting of an amino acid sequence of IDSGGADT (SEQ ID NO: 124), and a CDR3 consisting of an amino acid sequence of TIGRSTSR (SEQ ID NO: 118).ATTORNEY DOCKET NO. VRD-021BWO1

[0027] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGSAG (SEQ ID NO: 122), a CDR2 consisting of an amino acid sequence of IDSGGTDT (SEQ ID NO: 123), and a CDR3 consisting of an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0028] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGSF (SEQ ID NO: 128), a CDR2 consisting of an amino acid sequence of DSGGTD (SEQ ID NO: 132), and a CDR3 consisting of an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0029] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGSF (SEQ IDATTORNEY DOCKET NO. VRD-021BWO1NO: 128), a CDR2 consisting of an amino acid sequence of DSGGAD (SEQ ID NO: 133), and a CDR3 consisting of an amino acid sequence of GRSASR (SEQ ID NO: 102).

[0030] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence of SSDGSG (SEQ ID NO: 134), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 consisting of an amino acid sequence of SSDGSG (SEQ ID NO: 134), and a CDR3 consisting of an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0031] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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 (SEQ ID NO: 135), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 consisting of an amino acid sequence of SSDASG (SEQ ID NO: 135), and a CDR3 consisting of an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0032] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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 CDR3ATTORNEY DOCKET NO. VRD-021BWO1 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 consisting of an amino acid sequence of SSDSSG (SEQ ID NO: 136), and a CDR3 consisting of an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0033] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFSFGSF (SEQ ID NO: 130), a CDR2 consisting of an amino acid sequence of DSGGAD (SEQ ID NO: 133), and a CDR3 consisting of an amino acid sequence of GRSTSR (SEQ ID NO: 104).

[0034] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, wherein the Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGSA (SEQ ID NO: 131), a CDR2 consisting of an amino acid sequence of DSGGTD (SEQ ID NO: 132), and a CDR3 consisting of an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0035] In some embodiments, the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 1-11. InATTORNEY DOCKET NO. VRD-021BWO1 some embodiments, the sdAb comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb comprises an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 1- 11. In some embodiments, the sdAb comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb comprises an amino acid sequence of any one of SEQ ID NOs: 1-11.

[0036] In some embodiments, the sdAb has an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb has an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb has an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb has an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb has an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb has an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb has an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb has an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb has an amino acid sequence of any one of SEQ ID NOs: 1-11. In some embodiments, the sdAb consists of an amino acid sequence of any one of SEQ ID NOs: 1-11.

[0037] 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 of SEQ ID NO: 1.ATTORNEY DOCKET NO. VRD-021BWO1

[0038] In some embodiments, the sdAb has 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 has an amino acid sequence at least 85% identical to SEQ ID NO: 1. In some embodiments, the sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 1. In some embodiments, the sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 1. In some embodiments, the sdAb has an amino acid sequence at least 96% identical to SEQ ID NO: 1. In some embodiments, the sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 1. In some embodiments, the sdAb has an amino acid sequence at least 98% identical to SEQ ID NO: 1. In some embodiments, the sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 1. In some embodiments, the sdAb has an amino acid sequence of SEQ ID NO: 1. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 1.

[0039] 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 of SEQ ID NO: 2.

[0040] In some embodiments, the sdAb has 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 has an amino acid sequence at least 85% identical to SEQ ID NO: 2. In some embodiments, the sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 2. In some embodiments, the sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 2. In some embodiments, the sdAb has an amino acid sequence at least 96% identical to SEQ ID NO: 2. In some embodiments, the sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 2. In some embodiments, the sdAb has an amino acid sequence at least 98% identical to SEQ ID NO: 2. In some embodiments, the sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 2. In some embodiments, the sdAb has an amino acidATTORNEY DOCKET NO. VRD-021BWO1 sequence of SEQ ID NO: 2. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 2.

[0041] 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 comprises 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 of SEQ ID NO: 3.

[0042] In some embodiments, the sdAb has 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 has an amino acid sequence at least 85% identical to SEQ ID NO: 3. In some embodiments, the sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 3. In some embodiments, the sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 3. In some embodiments, the sdAb has an amino acid sequence at least 96% identical to SEQ ID NO: 3. In some embodiments, the sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 3. In some embodiments, the sdAb has an amino acid sequence at least 98% identical to SEQ ID NO: 3. In some embodiments, the sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 3. In some embodiments, the sdAb has an amino acid sequence of SEQ ID NO: 3. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 3.

[0043] 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, theATTORNEY DOCKET NO. VRD-021BWO1 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 of SEQ ID NO: 4.

[0044] In some embodiments, the sdAb has 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 has an amino acid sequence at least 85% identical to SEQ ID NO: 4. In some embodiments, the sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 4. In some embodiments, the sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 4. In some embodiments, the sdAb has an amino acid sequence at least 96% identical to SEQ ID NO: 4. In some embodiments, the sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 4. In some embodiments, the sdAb has an amino acid sequence at least 98% identical to SEQ ID NO: 4. In some embodiments, the sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 4. In some embodiments, the sdAb has an amino acid sequence of SEQ ID NO: 4. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 4.

[0045] 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 of SEQ ID NO: 5.

[0046] In some embodiments, the sdAb has 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 has an amino acid sequence at least 85% identical to SEQ ID NO: 5. In some embodiments, the sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 5. In some embodiments, the sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 5. In some embodiments, the sdAb has an amino acid sequence at least 96% identical to SEQ ID NO: 5. In some embodiments, the sdAb has an amino acid sequence at least 97% identical toATTORNEY DOCKET NO. VRD-021BWO1SEQ ID NO: 5. In some embodiments, the sdAb has an amino acid sequence at least 98% identical to SEQ ID NO: 5. In some embodiments, the sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 5. In some embodiments, the sdAb has an amino acid sequence of SEQ ID NO: 5. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 5.

[0047] 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 ID NO: 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 of SEQ ID NO: 6.

[0048] In some embodiments, the sdAb has 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 has an amino acid sequence at least 85% identical to SEQ ID NO: 6. In some embodiments, the sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 6. In some embodiments, the sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 6. In some embodiments, the sdAb has an amino acid sequence at least 96% identical to SEQ ID NO: 6. In some embodiments, the sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 6. In some embodiments, the sdAb has an amino acid sequence at least 98% identical to SEQ ID NO: 6. In some embodiments, the sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 6. In some embodiments, the sdAb has an amino acid sequence of SEQ ID NO: 6. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 6.

[0049] 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%ATTORNEY DOCKET NO. VRD-021BWO1 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 of SEQ ID NO: 7.

[0050] In some embodiments, the sdAb has 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 has an amino acid sequence at least 85% identical to SEQ ID NO: 7. In some embodiments, the sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 7. In some embodiments, the sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 7. In some embodiments, the sdAb has an amino acid sequence at least 96% identical to SEQ ID NO: 7. In some embodiments, the sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 7. In some embodiments, the sdAb has an amino acid sequence at least 98% identical to SEQ ID NO: 7. In some embodiments, the sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 7. In some embodiments, the sdAb has an amino acid sequence of SEQ ID NO: 7. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 7.

[0051] 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 of SEQ ID NO: 8.

[0052] In some embodiments, the sdAb has 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 has an amino acid sequence at least 85% identical to SEQ ID NO: 8. In some embodiments, the sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 8. In someATTORNEY DOCKET NO. VRD-021BWO1 embodiments, the sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 8. In some embodiments, the sdAb has an amino acid sequence at least 96% identical to SEQ ID NO: 8. In some embodiments, the sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 8. In some embodiments, the sdAb has an amino acid sequence at least 98% identical to SEQ ID NO: 8. In some embodiments, the sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 8. In some embodiments, the sdAb has an amino acid sequence of SEQ ID NO: 8. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 8.

[0053] 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 of SEQ ID NO: 9.

[0054] In some embodiments, the sdAb has 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 has an amino acid sequence at least 85% identical to SEQ ID NO: 9. In some embodiments, the sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 9. In some embodiments, the sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 9. In some embodiments, the sdAb has an amino acid sequence at least 96% identical to SEQ ID NO: 9. In some embodiments, the sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 9. In some embodiments, the sdAb has an amino acid sequence at least 98% identical to SEQ ID NO: 9. In some embodiments, the sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 9. In some embodiments, the sdAb has an amino acid sequence of SEQ ID NO: 9. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 9.

[0055] 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, theATTORNEY DOCKET NO. VRD-021BWO1 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 of SEQ ID NO: 10.

[0056] In some embodiments, the sdAb has 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 has an amino acid sequence at least 85% identical to SEQ ID NO: 10. In some embodiments, the sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 10. In some embodiments, the sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 10. In some embodiments, the sdAb has an amino acid sequence at least 96% identical to SEQ ID NO: 10. In some embodiments, the sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 10. In some embodiments, the sdAb has an amino acid sequence at least 98% identical to SEQ ID NO: 10. In some embodiments, the sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 10. In some embodiments, the sdAb has an amino acid sequence of SEQ ID NO: 10. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 10.

[0057] 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 ID NO: 11. In some embodiments, the sdAb comprises an amino acid sequence at least 99%ATTORNEY DOCKET NO. VRD-021BWO1 identical to SEQ ID NO: 11. In some embodiments, the sdAb comprises an amino acid sequence of SEQ ID NO: 11.

[0058] In some embodiments, the sdAb has 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 has an amino acid sequence at least 85% identical to SEQ ID NO: 11. In some embodiments, the sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 11. In some embodiments, the sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 11. In some embodiments, the sdAb has an amino acid sequence at least 96% identical to SEQ ID NO: 11. In some embodiments, the sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 11. In some embodiments, the sdAb has an amino acid sequence at least 98% identical to SEQ ID NO: 11. In some embodiments, the sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 11. In some embodiments, the sdAb has an amino acid sequence of SEQ ID NO: 11. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 11.

[0059] In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively), when produced in a recombinant cell (e.g., CHO cell), results in a yield of at least 400 mg / mL. In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has low self-interaction, for example, a wavelength shift of 1 nm or less using affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS). In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a DNA score of less than 3, for example, according to a polyreactive ELISA.

[0060] In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a Tmof at least 55°C (e.g., at least 56°C, at least 57°C, at least 58°C, at least 59°C, or at least 60°C). In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a Tmof at least 55°C. In some embodiments, an anti- HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a Tmof at least 56°C. In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a Tmof at least 57°C. In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a Tmof at least 58°C.ATTORNEY DOCKET NO. VRD-021BWO1In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a Tmof at least 59°C. In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a Tmof at least 60°C.

[0061] In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a Tagg266 of at least 65°C (e.g., at least 66°C, at least 68°C, or least 70°C). In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a Tagg266 of at least 65°C. In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a Tagg266 of at least 66°C. In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a Tagg266 of at least 68°C. In some embodiments, an anti-HSA sdAb described herein (e.g., a sdAb comprising CDRs of SEQ ID NOs: 91, 95, and 101, respectively) has a Tagg266 of at least 70°C.

[0062] In some embodiments, the present invention provides, among other things, a molecule comprising the fusion protein described herein.

[0063] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, and a second polypeptide comprising a second Fc region. In some embodiments, the sdAb comprises the sdAb described herein. In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the sdAb comprises the sdAb described herein. In some embodiments, the anti-HSA sdAb is fused to the C-terminus of the Fc region. In some embodiments, the anti-HSA sdAb is fused to the N-terminus of the Fc region.

[0064] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a single domain antibody (sdAb) that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein the sdAb comprises a CDR1 comprising an aminoATTORNEY DOCKET NO. VRD-021BWO1 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 sdAb comprises a CDR1 consisting of an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 consisting of an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 consisting of an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0065] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 consisting of an amino acid sequence of AIDSGGADTRYAESVKG (SEQ ID NO: 96), and a CDR3 consisting of an amino acid sequence of GRSASR (SEQ ID NO: 102).

[0066] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of QFGMS (SEQ ID NO: 92), a CDR2 consisting of an amino acid sequence of AISSDGSGTIYADSVKG (SEQ ID NO: 97), and a CDR3 consisting of an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).ATTORNEY DOCKET NO. VRD-021BWO1

[0067] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of QFGMS (SEQ ID NO: 92), a CDR2 consisting of an amino acid sequence of AISSDASGTIYADSVKG (SEQ ID NO: 98), and a CDR3 consisting of an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0068] In one aspect, the present invention provides, among other things, a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of QFGMS (SEQ ID NO: 92), a CDR2 consisting of an amino acid sequence of AISSDSSGTIYADSVKG (SEQ ID NO: 99), and a CDR3 consisting of an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0069] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein the sdAb comprises a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acid sequence ofATTORNEY DOCKET NO. VRD-021BWO1AIDSGGADTRYAETVKG (SEQ ID NO: 100), and a CDR3 comprising an amino acid sequence of GRSTSR (SEQ ID NO: 104). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 consisting of an amino acid sequence of AIDSGGADTRYAETVKG (SEQ ID NO: 100), and a CDR3 consisting of an amino acid sequence of GRSTSR (SEQ ID NO: 104).

[0070] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of SAGMS (SEQ ID NO: 93), a CDR2 consisting of an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 consisting of an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0071] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of SFGAS (SEQ ID NO: 94), a CDR2 consisting of an amino acid sequence of AIDSGGTDTRYAESIKG (SEQ ID NO: 95), and a CDR3 consisting of an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0072] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA,ATTORNEY DOCKET NO. VRD-021BWO1 and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 consisting of an amino acid sequence of AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 consisting of an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0073] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein the sdAb comprises a CDR1 comprising an amino acid sequence of AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence of AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence of TIGRSASR (SEQ ID NO: 116). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 consisting of an amino acid sequence of AIDSGGADTR (SEQ ID NO: 111), and a CDR3 consisting of an amino acid sequence of TIGRSASR (SEQ ID NO: 116).

[0074] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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 ofATTORNEY DOCKET NO. VRD-021BWO1TIGSSTTPSG (SEQ ID NO: 117). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 consisting of an amino acid sequence of AISSDGSGTI (SEQ ID NO: 112), and a CDR3 consisting of an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0075] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 consisting of an amino acid sequence of AISSDASGTI (SEQ ID NO: 113), and a CDR3 consisting of an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0076] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGQFGMS (SEQ ID NO: 106), a CDR2 consisting of an amino acid sequence of AISSDSSGTI (SEQ ID NO: 114), and a CDR3 consisting of an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0077] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / orATTORNEY DOCKET NO. VRD-021BWO1 the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFSFGSFGMS (SEQ ID NO: 107), a CDR2 consisting of an amino acid sequence of AIDSGGADTR (SEQ ID NO: 111), and a CDR3 consisting of an amino acid sequence of TIGRSTSR (SEQ ID NO: 118).

[0078] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of AASGFTFGSAGMS (SEQ ID NO: 108), a CDR2 consisting of an amino acid sequence of AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 consisting of an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0079] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1ATTORNEY DOCKET NO. VRD-021BWO1 consisting of an amino acid sequence of AASGFTFGSFGAS (SEQ ID NO: 109), a CDR2 consisting of an amino acid sequence of AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 consisting of an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0080] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGSFG (SEQ ID NO: 119), a CDR2 consisting of an amino acid sequence of IDSGGTDT (SEQ ID NO: 123), and a CDR3 consisting of an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0081] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGSFG (SEQ ID NO: 119), a CDR2 consisting of an amino acid sequence of IDSGGADT (SEQ ID NO: 124), and a CDR3 consisting of an amino acid sequence of TIGRSASR (SEQ ID NO: 116).

[0082] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311,ATTORNEY DOCKET NO. VRD-021BWO1428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGQFG (SEQ ID NO: 120), a CDR2 consisting of an amino acid sequence of ISSDGSGT (SEQ ID NO: 125), and a CDR3 consisting of an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0083] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGQFG (SEQ ID NO: 120), a CDR2 consisting of an amino acid sequence of ISSDASGT (SEQ ID NO: 126), and a CDR3 consisting of an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0084] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGQFG (SEQ ID NO: 120), a CDR2 consisting of an amino acid sequenceATTORNEY DOCKET NO. VRD-021BWO1 of ISSDSSGT (SEQ ID NO: 127), and a CDR3 consisting of an amino acid sequence of TIGSSTTPSG (SEQ ID NO: 117).

[0085] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFSFGSFG (SEQ ID NO: 121), a CDR2 consisting of an amino acid sequence of IDSGGADT (SEQ ID NO: 124), and a CDR3 consisting of an amino acid sequence of TIGRSTSR (SEQ ID NO: 118).

[0086] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGSAG (SEQ ID NO: 122), a CDR2 consisting of an amino acid sequence of IDSGGTDT (SEQ ID NO: 123), and a CDR3 consisting of an amino acid sequence of TIGQSTSR (SEQ ID NO: 115).

[0087] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; orATTORNEY DOCKET NO. VRD-021BWO1252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGSF (SEQ ID NO: 128), a CDR2 consisting of an amino acid sequence of DSGGTD (SEQ ID NO: 132), and a CDR3 consisting of an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0088] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGSF (SEQ ID NO: 128), a CDR2 consisting of an amino acid sequence of DSGGAD (SEQ ID NO: 133), and a CDR3 consisting of an amino acid sequence of GRSASR (SEQ ID NO: 102).

[0089] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein the sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence of SSDGSG (SEQ ID NO: 134), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 consisting of an amino acid sequence ofATTORNEY DOCKET NO. VRD-021BWO1SSDGSG (SEQ ID NO: 134), and a CDR3 consisting of an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0090] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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 (SEQ ID NO: 135), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 consisting of an amino acid sequence of SSDASG (SEQ ID NO: 135), and a CDR3 consisting of an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0091] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 consisting of an amino acid sequence of SSDSSG (SEQ ID NO: 136), and a CDR3 consisting of an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0092] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; orATTORNEY DOCKET NO. VRD-021BWO1252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFSFGSF (SEQ ID NO: 130), a CDR2 consisting of an amino acid sequence of DSGGAD (SEQ ID NO: 133), and a CDR3 consisting of an amino acid sequence of GRSTSR (SEQ ID NO: 104).

[0093] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to a sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions 252, 254, 256, 309, 311, 428, 433, and / or 434; 252, 254, 256, 433, and / or 434; 252, 254, 256, 428, 433, and / or 434; or 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein 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). In some embodiments, the sdAb comprises a CDR1 consisting of an amino acid sequence of GFTFGSA (SEQ ID NO: 131), a CDR2 consisting of an amino acid sequence of DSGGTD (SEQ ID NO: 132), and a CDR3 consisting of an amino acid sequence of GQSTSR (SEQ ID NO: 101).

[0094] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.

[0095] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E,ATTORNEY DOCKET NO. VRD-021BWO1428L, 433K, and 434F, and 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.

[0096] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.

[0097] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.

[0098] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.ATTORNEY DOCKET NO. VRD-021BWO1

[0099] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.

[0100] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.

[0101] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.

[0102] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and 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 acidATTORNEY DOCKET NO. VRD-021BWO1 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.

[0103] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and 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); 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.

[0104] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and 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); 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.

[0105] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and 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); 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.

[0106] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E,ATTORNEY DOCKET NO. VRD-021BWO1433K, and 434Y, and 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); 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.

[0107] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and 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); 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.

[0108] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and 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); 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.

[0109] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and 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); 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.ATTORNEY DOCKET NO. VRD-021BWO1

[0110] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.[OHl] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.

[0112] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.

[0113] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and 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); and a second polypeptide comprising a second Fc region,ATTORNEY DOCKET NO. VRD-021BWO1 wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y.

[0114] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and 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); 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.

[0115] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and 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); 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.

[0116] 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 describedATTORNEY DOCKET NO. VRD-021BWO1 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 of any one of SEQ ID NOs: 13-38.

[0117] 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 75% 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 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 amino acid sequence at least 99% identical to SEQ ID NO: 18. In some embodiments, the Fc region comprises an amino acid sequence of SEQ ID NO: 18.

[0118] 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 75% 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 amino 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 of SEQ ID NO: 20.

[0119] 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 aminoATTORNEY DOCKET NO. VRD-021BWO1 acid sequence at least 75% 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 least 99% identical to SEQ ID NO: 34. In some embodiments, the Fc region comprises an amino acid sequence of SEQ ID NO: 34.

[0120] 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 75% 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 of SEQ ID NO: 35.

[0121] In some embodiments, the fusion protein further comprises a linker. In some embodiments, the molecule further comprises a linker. In some embodiments, the linker is between the anti-HSA sdAb and the therapeutic protein. In some embodiments, the linker is between the anti-HSA sdAb and the Fc region.

[0122] 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: 139). In some embodiments, the linker comprises one unit of GGGGS (SEQ ID NO: 139). InATTORNEY DOCKET NO. VRD-021BWO1 some embodiments, the linker comprises at least 2 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises at least 3 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises at least 4 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises at least 5 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises at least 6 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises at least 7 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises at least 8 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises at least 9 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises at least 10 repeating units of GGGGS (SEQ ID NO: 139).

[0123] In some embodiments, the linker comprises 2 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises 3 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises 4 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises 5 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises 6 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises 7 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises 8 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises 9 repeating units of GGGGS (SEQ ID NO: 139). In some embodiments, the linker comprises 10 repeating units of GGGGS (SEQ ID NO: 139).

[0124] In some embodiments, the fusion protein comprises, from N-terminal to C- terminal, the anti-HSA sdAb, the linker, and the Fc region. In some embodiments, the fusion protein comprises, from N-terminal to C-terminal, the Fc region, the linker, and the anti-HSA sdAb.

[0125] In some embodiments, the anti-HSA sdAb is fused to the C-terminus of the Fc region. In some embodiments, the anti-HSA sdAb is fused to the N-terminus of the Fc region.

[0126] 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.ATTORNEY DOCKET NO. VRD-021BWO1

[0127] 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.

[0128] 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.

[0129] 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, 433K, 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.

[0130] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises aminoATTORNEY DOCKET NO. VRD-021BWO1 acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and the anti-HSA sdAb comprises (1) 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 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); (3) 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); or (4) 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).

[0131] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and the anti-HSA sdAb comprises (1) 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 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); (3) 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); (4) 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); (5) 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); (6) 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 acidATTORNEY DOCKET NO. VRD-021BWO1 sequence of GRSTSR (SEQ ID NO: 104); (7) 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); or (8) 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).

[0132] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions ofATTORNEY DOCKET NO. VRD-021BWO1252Y, 254T, 256E, 428L, 433K, and 434F, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and the anti-HSA 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).

[0133] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and the anti-HSA sdAb comprises (1) 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 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); (3) 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 anATTORNEY DOCKET NO. VRD-021BWO1 amino acid sequence of TIGQSTSR (SEQ ID NO: 115); or (4) 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).

[0134] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and the anti-HSA sdAb comprises (1) 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 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); (3) 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); (4) 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); (5) 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); (6) 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); (7) 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); or (8) 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).

[0135] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises aminoATTORNEY DOCKET NO. VRD-021BWO1 acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and the anti-HSA 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 acidATTORNEY DOCKET NO. VRD-021BWO1 sequence of GRSTSR (SEQ ID NO: 104). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and the anti-HSA 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). In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and the anti-HSA 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).

[0136] In some embodiments, the fusion protein forms a homodimer.

[0137] In some embodiments, the fusion protein forms a heterodimer. In some embodiments, the fusion protein forms a heterodimer with a second Fc region. In some embodiments, the second Fc region comprises the same amino acid substitutions as the first Fc region. In some embodiments, the second Fc region comprises different amino acid substitutions from the first Fc region.

[0138] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and the anti-HSA sdAb comprises (1) 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 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); (3) 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); or (4) 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 ofATTORNEY DOCKET NO. VRD-021BWO1GQSTSR (SEQ ID NO: 101); wherein the fusion protein forms a heterodimer with a second Fc region, and wherein the second Fc region comprises an amino acid sequence selected from SEQ ID NOs: 13-38.

[0139] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F, and the anti-HSA sdAb comprises (1) 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 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); (3) 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); (4) 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); (5) 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); (6) 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); (7) 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); or (8) 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) ; wherein the fusion protein forms a heterodimer with a second Fc region, and wherein the second Fc region comprises an amino acid sequence selected from SEQ ID NOs: 13-38.ATTORNEY DOCKET NO. VRD-021BWO1

[0140] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and the anti-HSA sdAb comprises (1) 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 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); (3) 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); or (4) 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); wherein the fusion protein forms a heterodimer with a second Fc region, and wherein the second Fc region comprises an amino acid sequence selected from SEQ ID NOs: 13-38.

[0141] In one aspect, the present invention provides, among other things, a fusion protein comprising an Fc region fused to an anti-HSA sdAb, wherein the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y, and the anti-HSA sdAb comprises (1) 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 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); (3) 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); (4) 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); (5) a CDR1 comprising an amino acid sequence of QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence ofATTORNEY DOCKET NO. VRD-021BWO1AISSDSSGTIYADSVKG (SEQ ID NO: 99), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103); (6) 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); (7) 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); or (8) 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); wherein the fusion protein forms a heterodimer with a second Fc region, and wherein the second Fc region comprises an amino acid sequence selected from SEQ ID NOs: 13-38.

[0142] In some embodiments, the Fc region further comprises knob-in-to-hole mutations. In some embodiments, the first Fc region further comprises a knob mutation, and the second Fc region further comprises a hole mutation. In some embodiments, the second Fc region further comprises a knob mutations, and the first Fc region further comprises a hole mutation.

[0143] In some embodiments, the knob-in-to-hole mutations comprise Y349C, T366S, L368A, and Y407V. In some embodiments, the knob-in-to-hole mutations comprise S354C and T366W. In some embodiments, the knob-in-to-hole mutations comprise T366S, L368A, and Y407V. In some embodiments, the knob-in-to-hole mutations comprise T366W.

[0144] In some embodiments, the knob mutation comprises one or more amino acid substitutions of (1) S354C and T366W; or (2) T366W. In some embodiments, the hole mutation comprises one or more amino acid substitutions of (1) Y349C, T366S, L368A, and Y407V; or (2) T366S, L368A, and Y407V.

[0145] In some embodiments, the fusion protein forms a heterodimer wherein the first Fc region comprises the knob-in-to-hole mutations of Y349C, T366S, L368A, and Y407V, and the second Fc region comprises the knob-in-to-hole mutations of S354C and T366W. In some embodiments, the fusion protein forms a heterodimer wherein first Fc region comprises the knob-in-to-hole mutations of T366S, L368A, and Y407V, and the second Fc region comprises the knob-in-to-hole mutation of T366W.

[0146] In some embodiments, the fusion protein comprises an amino acid sequence at least 70% identical to any one of SEQ ID NOs: 43-67 or 70-90. In some embodiments, theATTORNEY DOCKET NO. VRD-021BWO1 fusion protein 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 fusion protein 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 fusion protein 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 fusion protein 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 fusion protein 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 fusion protein 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 fusion protein 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 fusion protein comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 43-67 or 70-90. In some embodiments, the fusion protein 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 fusion protein comprises an amino acid sequence of any one of SEQ ID NOs: 43-67 or 70-90.

[0147] In some embodiments, the fusion protein comprises an amino acid sequence at least 70% identical to SEQ ID NO: 55. In some embodiments, the fusion protein comprises an amino acid sequence at least 75% identical to SEQ ID NO: 55. In some embodiments, the fusion protein comprises an amino acid sequence at least 80% identical to SEQ ID NO: 55. In some embodiments, the fusion protein comprises an amino acid sequence at least 85% identical to SEQ ID NO: 55. In some embodiments, the fusion protein comprises an amino acid sequence at least 90% identical to SEQ ID NO: 55. In some embodiments, the fusion protein comprises an amino acid sequence at least 95% identical to SEQ ID NO: 55. In some embodiments, the fusion protein comprises an amino acid sequence at least 96% identical to SEQ ID NO: 55. In some embodiments, the fusion protein comprises an amino acid sequence at least 97% identical to SEQ ID NO: 55. In some embodiments, the fusion protein comprises an amino acid sequence at least 98% identical to SEQ ID NO: 55. In some embodiments, the fusion protein comprises an amino acid sequence at least 99% identical to SEQ ID NO: 55. In some embodiments, the fusion protein comprises an amino acid sequence of SEQ ID NO: 55.

[0148] In some embodiments, the fusion protein comprises an amino acid sequence at least 70% identical to SEQ ID NO: 56. In some embodiments, the fusion protein comprises an amino acid sequence at least 75% identical to SEQ ID NO: 56. In some embodiments, theATTORNEY DOCKET NO. VRD-021BWO1 fusion protein comprises an amino acid sequence at least 80% identical to SEQ ID NO: 56. In some embodiments, the fusion protein comprises an amino acid sequence at least 85% identical to SEQ ID NO: 56. In some embodiments, the fusion protein comprises an amino acid sequence at least 90% identical to SEQ ID NO: 56. In some embodiments, the fusion protein comprises an amino acid sequence at least 95% identical to SEQ ID NO: 56. In some embodiments, the fusion protein comprises an amino acid sequence at least 96% identical to SEQ ID NO: 56. In some embodiments, the fusion protein comprises an amino acid sequence at least 97% identical to SEQ ID NO: 56. In some embodiments, the fusion protein comprises an amino acid sequence at least 98% identical to SEQ ID NO: 56. In some embodiments, the fusion protein comprises an amino acid sequence at least 99% identical to SEQ ID NO: 56. In some embodiments, the fusion protein comprises an amino acid sequence of SEQ ID NO: 56.

[0149] In some embodiments, the fusion protein comprises an amino acid sequence at least 70% identical to SEQ ID NO: 58. In some embodiments, the fusion protein comprises an amino acid sequence at least 75% identical to SEQ ID NO: 58. In some embodiments, the fusion protein comprises an amino acid sequence at least 80% identical to SEQ ID NO: 58. In some embodiments, the fusion protein comprises an amino acid sequence at least 85% identical to SEQ ID NO: 58. In some embodiments, the fusion protein comprises an amino acid sequence at least 90% identical to SEQ ID NO: 58. In some embodiments, the fusion protein comprises an amino acid sequence at least 95% identical to SEQ ID NO: 58. In some embodiments, the fusion protein comprises an amino acid sequence at least 96% identical to SEQ ID NO: 58. In some embodiments, the fusion protein comprises an amino acid sequence at least 97% identical to SEQ ID NO: 58. In some embodiments, the fusion protein comprises an amino acid sequence at least 98% identical to SEQ ID NO: 58. In some embodiments, the fusion protein comprises an amino acid sequence at least 99% identical to SEQ ID NO: 58. In some embodiments, the fusion protein comprises an amino acid sequence of SEQ ID NO: 58.

[0150] In some embodiments, the fusion protein comprises an amino acid sequence at least 70% identical to SEQ ID NO: 59. In some embodiments, the fusion protein comprises an amino acid sequence at least 75% identical to SEQ ID NO: 59. In some embodiments, the fusion protein comprises an amino acid sequence at least 80% identical to SEQ ID NO: 59. In some embodiments, the fusion protein comprises an amino acid sequence at least 85% identical to SEQ ID NO: 59. In some embodiments, the fusion protein comprises an amino acid sequence at least 90% identical to SEQ ID NO: 59. In some embodiments, the fusion protein comprises an amino acid sequence at least 95% identical to SEQ ID NO: 59. In someATTORNEY DOCKET NO. VRD-021BWO1 embodiments, the fusion protein comprises an amino acid sequence at least 96% identical to SEQ ID NO: 59. In some embodiments, the fusion protein comprises an amino acid sequence at least 97% identical to SEQ ID NO: 59. In some embodiments, the fusion protein comprises an amino acid sequence at least 98% identical to SEQ ID NO: 59. In some embodiments, the fusion protein comprises an amino acid sequence at least 99% identical to SEQ ID NO: 59. In some embodiments, the fusion protein comprises an amino acid sequence of SEQ ID NO: 59.

[0151] In some embodiments, the second Fc region comprises an amino acid sequence at least 70% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the second Fc region comprises an amino acid sequence at least 75% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the second Fc region comprises an amino acid sequence at least 80% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the second Fc region comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the second Fc region comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the second Fc region comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the second Fc region comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the second Fc region comprises an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the second Fc region comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the second Fc region comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 13-38. In some embodiments, the second Fc region comprises an amino acid sequence of any one of SEQ ID NOs: 13-38.

[0152] In some embodiments, the second Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 19. In some embodiments, the second Fc region comprises an amino acid sequence at least 75% identical to SEQ ID NO: 19. In some embodiments, the second Fc region comprises an amino acid sequence at least 80% 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 FcATTORNEY DOCKET NO. VRD-021BWO1 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 of SEQ ID NO: 19.

[0153] In some embodiments, the second Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 21. In some embodiments, the second Fc region comprises an amino acid sequence at least 75% identical to SEQ ID NO: 21. In some embodiments, the second Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 21. In some embodiments, the second Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 21. In some embodiments, the second Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 21. In some embodiments, the second Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 21. In some embodiments, the second Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 21. In some embodiments, the second Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 21. In some embodiments, the second Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 21. In some embodiments, the second Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 21. In some embodiments, the second Fc region comprises an amino acid sequence of SEQ ID NO: 21.

[0154] In some embodiments, the second Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 75% identical to SEQ ID NO: 37. In some embodiments, the second Fc region comprises an amino acid sequence at least 80% 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 Fc 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 acidATTORNEY DOCKET NO. VRD-021BWO1 sequence at least 99% identical to SEQ ID NO: 37. In some embodiments, the second Fc region comprises an amino acid sequence of SEQ ID NO: 37.

[0155] In some embodiments, the second Fc region comprises an amino acid sequence at least 70% identical to SEQ ID NO: 38. In some embodiments, the second Fc region comprises an amino acid sequence at least 75% identical to SEQ ID NO: 38. In some embodiments, the second Fc region comprises an amino acid sequence at least 80% identical to SEQ ID NO: 38. In some embodiments, the second Fc region comprises an amino acid sequence at least 85% identical to SEQ ID NO: 38. In some embodiments, the second Fc region comprises an amino acid sequence at least 90% identical to SEQ ID NO: 38. In some embodiments, the second Fc region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 38. In some embodiments, the second Fc region comprises an amino acid sequence at least 96% identical to SEQ ID NO: 38. In some embodiments, the second Fc region comprises an amino acid sequence at least 97% identical to SEQ ID NO: 38. In some embodiments, the second Fc region comprises an amino acid sequence at least 98% identical to SEQ ID NO: 38. In some embodiments, the second Fc region comprises an amino acid sequence at least 99% identical to SEQ ID NO: 38. In some embodiments, the second Fc region comprises an amino acid sequence of SEQ ID NO: 38.

[0156] In some embodiments, a first polypeptide comprises an amino acid sequence at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 43-67 or 70-90. In some embodiments, a first polypeptide comprises an amino acid sequence at least 60% identical to SEQ ID NOs: 43-67 or 70-90. In some embodiments, a first polypeptide comprises an amino acid sequence at least 70% identical to SEQ ID NOs: 43-67 or 70-90. In some embodiments, a first polypeptide comprises an amino acid sequence at least 80% identical to SEQ ID NOs: 43-67 or 70-90. In some embodiments, a first polypeptide comprises an amino acid sequence at least 85% identical to SEQ ID NOs: 43-67 or 70-90. In some embodiments, a first polypeptide comprises an amino acid sequence at least 90% identical to SEQ ID NOs: 43-67 or 70-90. In some embodiments a first polypeptide comprises an amino acid sequence at least 95% identical to SEQ ID NOs: 43-67 or 70-90. In some embodiments, a first polypeptide comprises an amino acid sequence at least 96% identical to SEQ ID NOs: 43-67 or 70-90. In some embodiments, a first polypeptide comprises an amino acid sequence at least 97% identical to SEQ ID NOs: 43-67 or 70-90. In some embodiments, a first polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NOs: 43-67 or 70-90. In some embodiments, a first polypeptideATTORNEY DOCKET NO. VRD-021BWO1 comprises an amino acid sequence at least 99% identical to SEQ ID NOs: 43-67 or 70-90. In some embodiments, a first polypeptide comprises an amino acid sequence of SEQ ID NOs: 43-67 or 70-90.

[0157] In some embodiments, a first polypeptide comprises an amino acid sequence at least 60% identical to SEQ ID NO: 55. In some embodiments, a first polypeptide comprises an amino acid sequence at least 70% identical to SEQ ID NO: 55. In some embodiments, a first polypeptide comprises an amino acid sequence at least 80% identical to SEQ ID NO: 55. In some embodiments, a first polypeptide comprises an amino acid sequence at least 85% identical to SEQ ID NO: 55. In some embodiments, a first polypeptide comprises an amino acid sequence at least 90% identical to SEQ ID NO: 55. In some embodiments a first polypeptide comprises an amino acid sequence at least 95% identical to SEQ ID NO: 55. In some embodiments, a first polypeptide comprises an amino acid sequence at least 96% identical to SEQ ID NO: 55. In some embodiments, a first polypeptide comprises an amino acid sequence at least 97% identical to SEQ ID NO: 55. In some embodiments, a first polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NO: 55. In some embodiments, a first polypeptide comprises an amino acid sequence at least 99% identical to SEQ ID NO: 55. In some embodiments, a first polypeptide comprises an amino acid sequence of SEQ ID NO: 55.

[0158] In some embodiments, a first polypeptide comprises an amino acid sequence at least 60% identical to SEQ ID NO: 56. In some embodiments, a first polypeptide comprises an amino acid sequence at least 70% identical to SEQ ID NO: 56. In some embodiments, a first polypeptide comprises an amino acid sequence at least 80% identical to SEQ ID NO: 56. In some embodiments, a first polypeptide comprises an amino acid sequence at least 85% identical to SEQ ID NO: 56. In some embodiments, a first polypeptide comprises an amino acid sequence at least 90% identical to SEQ ID NO: 56. In some embodiments a first polypeptide comprises an amino acid sequence at least 95% identical to SEQ ID NO: 56. In some embodiments, a first polypeptide comprises an amino acid sequence at least 96% identical to SEQ ID NO: 56. In some embodiments, a first polypeptide comprises an amino acid sequence at least 97% identical to SEQ ID NO: 56. In some embodiments, a first polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NO: 56. In some embodiments, a first polypeptide comprises an amino acid sequence at least 99% identical to SEQ ID NO: 56. In some embodiments, a first polypeptide comprises an amino acid sequence of SEQ ID NO: 56.ATTORNEY DOCKET NO. VRD-021BWO1

[0159] In some embodiments, a first polypeptide comprises an amino acid sequence at least 60% identical to SEQ ID NO: 58. In some embodiments, a first polypeptide comprises an amino acid sequence at least 70% identical to SEQ ID NO: 58. In some embodiments, a first polypeptide comprises an amino acid sequence at least 80% identical to SEQ ID NO: 58. In some embodiments, a first polypeptide comprises an amino acid sequence at least 85% identical to SEQ ID NO: 58. In some embodiments, a first polypeptide comprises an amino acid sequence at least 90% identical to SEQ ID NO: 58. In some embodiments a first polypeptide comprises an amino acid sequence at least 95% identical to SEQ ID NO: 58. In some embodiments, a first polypeptide comprises an amino acid sequence at least 96% identical to SEQ ID NO: 58. In some embodiments, a first polypeptide comprises an amino acid sequence at least 97% identical to SEQ ID NO: 58. In some embodiments, a first polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NO: 58. In some embodiments, a first polypeptide comprises an amino acid sequence at least 99% identical to SEQ ID NO: 58. In some embodiments, a first polypeptide comprises an amino acid sequence of SEQ ID NO: 58.

[0160] In some embodiments, a first polypeptide comprises an amino acid sequence at least 60% identical to SEQ ID NO: 59. In some embodiments, a first polypeptide comprises an amino acid sequence at least 70% identical to SEQ ID NO: 59. In some embodiments, a first polypeptide comprises an amino acid sequence at least 80% identical to SEQ ID NO: 59. In some embodiments, a first polypeptide comprises an amino acid sequence at least 85% identical to SEQ ID NO: 59. In some embodiments, a first polypeptide comprises an amino acid sequence at least 90% identical to SEQ ID NO: 59. In some embodiments a first polypeptide comprises an amino acid sequence at least 95% identical to SEQ ID NO: 59. In some embodiments, a first polypeptide comprises an amino acid sequence at least 96% identical to SEQ ID NO: 59. In some embodiments, a first polypeptide comprises an amino acid sequence at least 97% identical to SEQ ID NO: 59. In some embodiments, a first polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NO: 59. In some embodiments, a first polypeptide comprises an amino acid sequence at least 99% identical to SEQ ID NO: 59. In some embodiments, a first polypeptide comprises an amino acid sequence of SEQ ID NO: 59.

[0161] In some embodiments, the fusion protein forms a homodimer. In some embodiments, the fusion protein forms a heterodimerATTORNEY DOCKET NO. VRD-021BWO1

[0162] In some embodiments, the fusion protein forms a heterodimer. In some embodiments, a molecule is a heterodimer. In some embodiments, a first polypeptide and a second polypeptide form a heterodimer. In some embodiments, the first Fc region forms a heterodimer with the second Fc region. In some embodiments, the first Fc region further comprises a knob mutation, and the second Fc region further comprises a hole mutation. In some embodiments, the second Fc region further comprises a knob mutation, and the first Fc region further comprises a hole mutation.

[0163] In one aspect, the present invention provides, among other things, a fusion protein comprising (1) a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, and (2) a second polypeptide comprising a second Fc region. In some embodiments, 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.

[0164] In some embodiments, the fusion protein binds to HSA with a lower KD at pH 6.0 as compared to a KD at pH 7.4. In some embodiments, the fusion protein binds to HSA with a KD of less than 500 nM at pH 6.0. In some embodiments, the fusion protein binds to HSA with a KD of less than 1000 nM at pH 7.4. In some embodiments, the fusion protein binds to HSA with a KD of -200 nM.

[0165] In some embodiments, the fusion protein blocks IgGs from binding to FcRn. In some embodiments, the fusion protein blocks or reduces naturally occurring recycling of IgGs. In some embodiments, the fusion protein results in increased catabolism of the IgGs. In some embodiments, the IgGs comprise pathogenic autoantibodies.

[0166] In some embodiments, the molecule binds to HSA with a lower KD at pH 6.0 as compared to a KD at pH 7.4. In some embodiments, the molecule binds to HSA with a KD of less than 500 nM at pH 6.0. In some embodiments, the molecule binds to HSA with a KD of less than 1000 nM at pH 7.4. In some embodiments, the molecule binds to HSA with a KD of -200 nM.

[0167] In some embodiments, the molecule blocks IgGs from binding to FcRn. In some embodiments, the molecule blocks or reduces naturally occurring recycling of IgGs. In some embodiments, the molecule results in increased catabolism of the IgGs. In some embodiments, the IgGs comprise pathogenic autoantibodies.

[0168] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, and a second polypeptide comprising a second Fc region. In some embodiments, theATTORNEY DOCKET NO. VRD-021BWO1 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.

[0169] In one aspect, the present invention provides, among other things, a molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, 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.

[0170] In one aspect, the present invention provides, among other things, a construct comprising a fusion protein comprising (1) a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, and (2) a second polypeptide comprising a second Fc region. In some embodiments, 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.

[0171] In one aspect, the present invention provides, among other things, a complex comprising a fusion protein comprising (1) a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, and (2) a second polypeptide comprising a second Fc region. In some embodiments, 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.

[0172] In some embodiments, the first polypeptide comprises, from N-terminal to C- terminal, the first Fc region, the linker, and the sdAb. In some embodiments, the first polypeptide comprises, from N-terminal to C-terminal, the sdAb, the linker, and the first Fc region.

[0173] In some embodiments, the present invention provides, among other things, nucleic acids encoding a fusion protein described herein. In some embodiments, the present invention provides, among other things, nucleic acids encoding a molecule described herein. In some embodiments, the present invention provides, among other things, a vector comprising the nucleic acid encoding the fusion protein. In some embodiments, the present invention provides, among other things, a vector comprising the nucleic acid encoding the molecule. In some embodiments, the present invention provides, among other things, a host cell comprising the nucleic acid or the vector.

[0174] In some embodiments, the pharmaceutical composition comprises the fusion protein described herein, and a pharmaceutically acceptable carrier. In some embodiments,ATTORNEY DOCKET NO. VRD-021BWO1 the pharmaceutical composition comprises the molecule described herein, and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition comprises the nucleic acid described herein, and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition comprises the vector described herein, and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition comprises the host cell described herein, and a pharmaceutically acceptable carrier.

[0175] In some embodiments, the present invention provides, among other things, a method of treating a disease or disorder in a subject in need thereof. In some embodiments, the method comprises administering to the subject fusion protein described herein. In some embodiments, the method comprises administering to the subject the molecule described herein. In some embodiments, the method comprises administering to the subject the pharmaceutical composition described herein.

[0176] In some embodiments, the present invention provides, among other things, a method of preventing a disease or disorder in a subject in need thereof. In some embodiments, the method comprises administering to the subject the fusion protein described herein. In some embodiments, the method comprises administering to the subject the molecule described herein. In some embodiments, the method comprises administering to the subject the pharmaceutical composition described herein.

[0177] In some embodiments, the disease or disorder is an autoimmune disease. 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.

[0178] 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 isATTORNEY DOCKET NO. VRD-021BWO1 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.

[0179] In some embodiments, the present invention provides, among other things, a method for treating a pathology associated with elevated levels of an IgG in a subject in need thereof. In some embodiments, the method comprises administering to the subject a therapeutically effective amount of the fusion protein described herein. In some embodiments, the method comprises administering to the subject a therapeutically effective amount of the molecule described herein. In some embodiments, the method comprises administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0180] In some embodiments, the present invention provides, among other things, a method for reducing biological activity of an IgG in a subject in need thereof. In some embodiments, the method comprises administering to the subject a therapeutically effective amount of the fusion protein described herein. In some embodiments, the method comprises administering to the subject a therapeutically effective amount of the molecule described herein. In some embodiments, the method comprises administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0181] In some embodiments, administration of the fusion protein reduces IgG levels to less than 60%, to less than 50%, to less than 40%, to less than 30%, or to less than 25% for at least 5 days, 7 days, 10 days, 15 days, or 20 days post administration.

[0182] In some embodiments, administration of the fusion protein reduces IgG levels to less than 60%. In some embodiments, administration of the fusion protein reduces IgG levelsATTORNEY DOCKET NO. VRD-021BWO1 to less than 50%. In some embodiments, administration of the fusion protein reduces IgG levels to less than 40%. In some embodiments, administration of the fusion protein reduces IgG levels to less than 30%. In some embodiments, administration of the fusion protein reduces IgG levels to less than 25%.

[0183] In some embodiments, administration of the molecule reduces IgG levels to less than 60%, to less than 50%, to less than 40%, to less than 30%, or to less than 25% for at least 5 days, 7 days, 10 days, 15 days, or 20 days post administration.

[0184] In some embodiments, administration of the molecule reduces IgG levels to less than 60%. In some embodiments, administration of the molecule reduces IgG levels to less than 50%. In some embodiments, administration of the molecule reduces IgG levels to less than 40%. In some embodiments, administration of the molecule reduces IgG levels to less than 30%. In some embodiments, administration of the molecule reduces IgG levels to less than 25%.

[0185] In some embodiments, administration of the pharmaceutical composition reduces IgG levels to less than 60%, to less than 50%, to less than 40%, to less than 30%, or to less than 25% for at least 5 days, 7 days, 10 days, 15 days, or 20 days post administration.

[0186] In some embodiments, administration of the pharmaceutical composition reduces IgG levels to less than 60%. In some embodiments, administration of the pharmaceutical composition reduces IgG levels to less than 50%. In some embodiments, administration of the pharmaceutical composition reduces IgG levels to less than 40%. In some embodiments, administration of the pharmaceutical composition reduces IgG levels to less than 30%. In some embodiments, administration of the pharmaceutical composition reduces IgG levels to less than 25%.

[0187] In some embodiments, the IgG levels are reduced for at least 5 days postadministration. In some embodiments, the IgG levels are reduced for at least 7 days postadministration. In some embodiments, the IgG levels are reduced for at least 10 days postadministration. In some embodiments, the IgG levels are reduced for at least 15 days postadministration. In some embodiments, the IgG levels are reduced for at least 20 days postadministration.

[0188] In some embodiments, the IgG levels are reduced as compared to a baseline. In some embodiments, the baseline is the IgG level in the patient prior to administration. In some embodiments, the baseline is the IgG level in a comparable patient without the administration of the fusion protein described herein. In some embodiments, the baseline isATTORNEY DOCKET NO. VRD-021BWO1 the IgG level in a comparable patient without the administration of the molecule described herein. In some embodiments, the baseline is the IgG level in a comparable patient without the administration of the pharmaceutical composition described herein.

[0189] In one aspect, the present invention provides, among other things, a method of producing a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, comprising introducing one or more amino acid additions, deletions, or substitutions to a reference sdAb, wherein the reference 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). In some embodiments, the reference sdAb comprises an amino acid sequence of SEQ ID NO: 1. In some embodiments, the reference sdAb consists of an amino acid sequence of SEQ ID NO: 1. In some embodiments, the reference sdAb comprises an amino acid sequence of SEQ ID NO: 2. In some embodiments, the reference sdAb consists of an amino acid sequence of SEQ ID NO: 2. In some embodiments, the reference sdAb comprises an amino acid sequence of SEQ ID NO: 3. In some embodiments, the reference sdAb consists of an amino acid sequence of SEQ ID NO: 3.

[0190] In one aspect, the present invention provides, among other things, a method of producing a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, comprising introducing one or more amino acid additions, deletions, or substitutions to a reference sdAb, wherein the reference 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). In some embodiments, the reference sdAb comprises an amino acid sequence of SEQ ID NO: 4. In some embodiments, the reference sdAb consists of an amino acid sequence of SEQ ID NO: 4.

[0191] In one aspect, the present invention provides, among other things, a method of producing a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, comprising introducing one or more amino acid additions, deletions, or substitutions to a reference sdAb, wherein the reference 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). In some embodiments, the reference sdAbATTORNEY DOCKET NO. VRD-021BWO1 comprises an amino acid sequence of SEQ ID NO: 5. In some embodiments, the reference sdAb consists of an amino acid sequence of SEQ ID NO: 5.

[0192] In one aspect, the present invention provides, among other things, a method of producing a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, comprising introducing one or more amino acid additions, deletions, or substitutions to a reference sdAb, the reference 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). In some embodiments, the reference sdAb comprises an amino acid sequence of SEQ ID NO: 6. In some embodiments, the reference sdAb consists of an amino acid sequence of SEQ ID NO: 6.

[0193] In one aspect, the present invention provides, among other things, a method of producing a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, comprising introducing one or more amino acid additions, deletions, or substitutions to a reference sdAb, wherein the reference 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). In some embodiments, the reference sdAb comprises an amino acid sequence of SEQ ID NO: 7. In some embodiments, the reference sdAb consists of an amino acid sequence of SEQ ID NO: 7.

[0194] In one aspect, the present invention provides, among other things, a method of producing a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, comprising introducing one or more amino acid additions, deletions, or substitutions to a reference sdAb, wherein the reference 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). In some embodiments, the reference sdAb comprises an amino acid sequence of SEQ ID NO: 8. In some embodiments, the reference sdAb consists of an amino acid sequence of SEQ ID NO: 8.

[0195] In one aspect, the present invention provides, among other things, a method of producing a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, comprising introducing one or more amino acid additions, deletions, or substitutions to a reference sdAb, wherein the reference sdAb comprises a CDR1 comprising an amino acidATTORNEY DOCKET NO. VRD-021BWO1 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). In some embodiments, the reference sdAb comprises an amino acid sequence of SEQ ID NO: 9. In some embodiments, the reference sdAb consists of an amino acid sequence of SEQ ID NO: 9. In some embodiments, the reference sdAb comprises an amino acid sequence of SEQ ID NO: 11. In some embodiments, the reference sdAb consists of an amino acid sequence of SEQ ID NO: 11.

[0196] In one aspect, the present invention provides, among other things, a method of producing a fusion protein comprising an Fc region fused to a sdAb that binds to HSA, comprising introducing one or more amino acid additions, deletions, or substitutions to a reference sdAb, wherein the reference 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. In some embodiments, the reference sdAb comprises an amino acid sequence of SEQ ID NO: 10. In some embodiments, the reference sdAb consists of an amino acid sequence of SEQ ID NO: 10.

[0197] In some embodiments, the method comprises introducing one or more amino acid additions to the reference sdAb. In some embodiments, the method comprises introducing one or more amino acid additions at the C-terminus of the reference sdAb. In some embodiments, the one or more amino acid additions is an addition of one or more alanine residues. In some embodiments, the method comprises introducing one or more additions of alanine residues at the C-terminus of the reference sdAb.

[0198] In some embodiments, the method comprises introducing one or more amino acid deletions to the reference sdAb.

[0199] In some embodiments, the method comprises introducing one or more amino acid substitutions to the reference sdAb. In some embodiments, the method comprises introducing one or more amino acid substitutions in the CDRs and / or framework regions of the reference sdAb. In some embodiments, the method comprises introducing one or more amino acid substitutions in the CDRs of the reference sdAb. In some embodiments, the method comprises introducing one or more amino acid substitutions in the framework regions of the reference sdAb. In some embodiments, the method comprises introducing one or more amino acid substitutions in the CDRs and framework regions of the reference sdAb. In someATTORNEY DOCKET NO. VRD-021BWO1 embodiments, the method comprises introducing one or more amino acid substitutions in the CDRs or framework regions of the reference sdAb.

[0200] In some embodiments, the one or more amino acid substitutions comprise F32A and / or M34A. In some embodiments, the one or more amino acid substitutions comprise F32A. In some embodiments, the one or more amino acid substitutions comprise M34A. In some embodiments, the one or more amino acid substitutions comprise F32A and M34A. In some embodiments, the one or more amino acid substitutions comprise F32A or M34A.

[0201] In one aspect, the present invention provides, among other things, an Fc-sdAb fusion produced by the method described herein. In some embodiments, the sdAb comprises as amino acid sequence of any one of SEQ ID NOs: 9-11.BRIEF DESCRIPTION OF THE DRAWINGS

[0202] The drawings are for illustration purposes only, and are not meant to be limiting.

[0203] FIG. 1 are exemplary graphs demonstrating the effects of exemplary anti-HSA fusion proteins on IgG reduction up to 14 days post-administration in a cynomolgus monkey model.

[0204] FIG. 2 is an exemplary graph illustrating the serum half-life of anti-HSA fusion proteins up to 14 days post-administration in a cynomolgus monkey model.

[0205] FIG. 3 are exemplary graphs visualizing the changes in albumin up to 14 days post-administration of exemplary anti-HSA fusion proteins in a cynomolgus monkey model.

[0206] FIG. 4 are exemplary graphs showing the changes in low density lipoprotein (LDL) up to 14 days post-administration of exemplary anti-HSA fusion proteins in a cynomolgus monkey model.

[0207] FIG. 5 is an exemplary graph demonstrating the effects of an exemplary anti-HSA fusion protein on IgG reduction up to 42 days post-administration in a cynomolgus monkey model.

[0208] FIG. 6 is an exemplary graph illustrating the serum half-life of an anti-HSA fusion protein up to 42 days post-administration in a cynomolgus monkey model.

[0209] FIG. 7 is an exemplary graph visualizing the changes in albumin up to 42 days post-administration of an exemplary anti-HSA fusion protein in a cynomolgus monkey model.ATTORNEY DOCKET NO. VRD-021BWO1

[0210] FIG. 8 is an exemplary graph showing the changes in low density lipoprotein (LDL) up to 42 days post-administration of an exemplary anti-HSA fusion protein in a cynomolgus monkey model.DEFINITIONS

[0211] 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.

[0212] 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. As used herein, an antibody fragment includes a monomeric heavy chain or monomeric light chain, or a fragment thereof.

[0213] 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.

[0214] 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 normal 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.

[0215] CDRs: As used herein, the term “CDR” refers to complementarity determining regions of an antibody or antigen binding fragment thereof. The CDRs are three flexibleATTORNEY DOCKET NO. VRD-021BWO1 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.

[0216] 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.

[0217] 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.

[0218] Fusion protein '. As used herein, the term “fusion protein” refers to two or more polypeptides in association. In some embodiments, a fusion protein refers to two or more polypeptides joined together by a linker. In some embodiments, a fusion protein refers to two or more polypeptides associated together by non-covalent interactions. In some embodiments, a fusion protein includes an anti-HSA sdAb fused to an Fc region. In some embodiments, a fusion protein includes a protein dimer formed by, for example and without limitation, (1) an anti-HSA sdAb fused to a first Fc region and (2) a second Fc region. The polypeptides that associate together to form a fusion protein may be referred to herein as “fusion partners”.

[0219] 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 applyATTORNEY DOCKET NO. VRD-021BWO1 as a parameter of the binding affinity of a targeting moiety to its cognate ligand for the subject compositions.

[0220] sdAb'. As used herein, the term “sdAb” also referred to as a single domain antibody, domain antibody, VHH, VNAR, nanobody or other grammatical equivalents, refers to an 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. In some embodiments, a sdAb comprises a constant region or an Fc region. In some embodiments, a sdAb is an antigen binding protein of a heavy chain only antibody or single domain antibody. In some embodiments, a sdAb is a binding protein (e.g., antibody, fragment thereof) comprising at least one monomeric domain, such as a VHH domain, devoid of a light chain, and, optionally, an Fc region. However, the sdAbs described herein may be used in any other antibody formats as a variable domain. In some embodiments, an sdAb is a monomer. In some embodiments, an sdAb is a homodimer. In some embodiments, an sdAb is a heterodimer.

[0221] In vitro'. As used herein, the term “in 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.

[0222] In vivo'. As used herein, the term “in 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).

[0223] 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.

[0224] 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-021BWO1 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

[0225] The present invention provides, among other things, single domain antibodies (sdAbs) that bind to human serum albumin (HSA) with high affinity. In some embodiments, the anti-HSA sdAbs described herein are fused to therapeutic proteins. In some embodiments, the anti-HSA sdAbs are fused to an Fc region. The anti-HSA sdAbs of the present invention prolong the serum half-life and increase the magnitude of effect of fusion partners without affecting serum albumin levels, effectively improving the therapeutic potential of the fusion partner without causing side effects.A. Human Serum Albumin (HSA)

[0226] Human serum albumin (HSA) is the most abundant protein in plasma and has several functions. HSA plays a role in maintaining osmotic pressure in blood vessels and plasma pH, but it also serves as a drug transport protein and carrier for many metabolites and fatty acids. Further, HSA has a serum half-life of approximately 3 -weeks, and association with therapeutic proteins has shown to significantly improve their serum half-life.

[0227] Described herein are anti-HSA single domain antibodies (sdAbs) that bind and recruit albumin to a fusion protein. The anti-HSA sdAbs are significantly smaller than albumin, which comprises 585 amino acids, and offer an alternative to direct conjugation of albumin to the therapeutic protein.B. Anti-HSA Antibodies

[0228] In one aspect, the present invention provides, among other things, single domain antibodies that bind to HSA. In some embodiments, the present invention provides albumin binding domains that can be adapted to various antibody formats.

[0229] A traditional antibody, also known as an immunoglobulin, is a Y-shaped structuring consisting of four polypeptides, two heavy chains and two light chains. The light chain consists of one variable region (VL) and one constant region (CL). The heavy chain consists of one variable region (VH) and at least three constant regions (CHI, CH2, CH3).ATTORNEY DOCKET NO. VRD-021BWO1The two light and two heavy chains are joined by disulfide bonds in the Y-shaped structure, with the light chains bracketing the heavy chains at the mouth of the Y-shape and continuing through the variable region. The variable regions determine the binding specificity of the antibody. Each variable region contains three hypervariable regions known as complementarity determining regions (CDRs) flanked by four relatively conserved regions known as framework regions (FRs). The three CDRs, referred to as CDR1, CDR2, and CDR3, contribute to the antibody binding specificity. Naturally occurring antibodies have often been used as starting material for engineered antibodies, such as chimeric antibodies and humanized antibodies. Examples of antibody-based antigen binding fragments include Fab, Fab’, (Fab’)2, Fv, single chain antibodies (e.g., scFv), minibodies, and diabodies. Examples of antibodies that have been modified or engineered include chimeric antibodies, humanized antibodies, and multispecific antibodies (e.g., bispecific antibodies).

[0230] Similarly, an anti-HSA sdAb described herein may be used in engineered antibodies or antibody-based antigen binding fragments. In some embodiments, the present invention provides, among other things, an anti-HSA antibody. In some embodiments, the present invention provides, among other things, an anti-HSA Fab. In some embodiments, the present invention provides, among other things, an anti-HSA Fab’. In some embodiments, the present invention provides, among other things, an anti-HSA (Fab’)2. In some embodiments, the present invention provides, among other things, an anti-HSA Fv. In some embodiments, the present invention provides, among other things, an anti-HSA single chain antibodies (e.g., scFv). In some embodiments, the present invention provides, among other things, anti-HSA minibodies. In some embodiments, the present invention provides, among other things, anti- HSA diabodies.Exemplary anti-HSA Binding Domains

[0231] In some embodiments, the anti-HSA sdAb is derived from a camelid VHH. In some embodiments, the anti-HSA sdAb is derived from a cartilaginous fish VNAR. In some embodiments, the anti-HSA sdAb is derived from a camelid VHH and humanized. In some embodiments, the anti-HSA sdAb is derived from a cartilaginous fish VNAR and humanized.

[0232] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence selected from Table Al. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60% identical to an amino acid sequence in Table Al. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 70% identical toATTORNEY DOCKET NO. VRD-021BWO1 an amino acid sequence in Table Al. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 80% identical to an amino acid sequence in Table Al. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to an amino acid sequence in Table Al. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to an amino acid sequence in Table Al. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to an amino acid sequence in Table Al. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to an amino acid sequence in Table Al. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to an amino acid sequence in Table Al. In some embodiments, the anti- HSA sdAb comprises an amino acid sequence at least 98% identical to an amino acid sequence in Table Al. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to an amino acid sequence in Table Al.Table Al. Exemplary amino acid sequences of anti-HSA sdAbs.

[0233] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence of any one of SEQ ID NOs: 1-11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60% identical to any one of SEQ ID NOs: 1-11. In someATTORNEY DOCKET NO. VRD-021BWO1 embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 70% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 80% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 98% identical to any one of SEQ ID NOs: 1-11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to any one of SEQ ID NOs: 1-11.

[0234] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60% identical to SEQ ID NO: 1. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 70% identical to SEQ ID NO: 1. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 80% identical to SEQ ID NO: 1. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 1. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 1. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 1. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 1. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 1. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 1. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 1. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence of SEQ ID NO: 1.

[0235] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60%ATTORNEY DOCKET NO. VRD-021BWO1 identical to SEQ ID NO: 2. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 70% identical to SEQ ID NO: 2. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 80% identical to SEQ ID NO: 2. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 2. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 2. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 2. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 2. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 2. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 2. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 2. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence of SEQ ID NO: 2.

[0236] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60% identical to SEQ ID NO: 3. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 70% identical to SEQ ID NO: 3. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 80% identical to SEQ ID NO: 3 In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 3. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 3. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 3. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 3. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 3. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 3. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 3. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence of SEQ ID NO: 3.

[0237] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60% identical to SEQ ID NO: 4. In some embodiments, the anti-HSA sdAb comprises an aminoATTORNEY DOCKET NO. VRD-021BWO1 acid sequence at least 70% identical to SEQ ID NO: 4. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 80% identical to SEQ ID NO: 4. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 4. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 4. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 4. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 4. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 4. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 4. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 4. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence of SEQ ID NO: 4.

[0238] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60% identical to SEQ ID NO: 5. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 70% identical to SEQ ID NO: 5. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 80% identical to SEQ ID NO: 5. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 5. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 5. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 5. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 5. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 5. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 5. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 5. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence of SEQ ID NO: 5.

[0239] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60% identical to SEQ ID NO: 6. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 70% identical to SEQ ID NO: 6. In some embodiments, the anti-HSAATTORNEY DOCKET NO. VRD-021BWO1 sdAb comprises an amino acid sequence at least 80% identical to SEQ ID NO: 6. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 6. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 6. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 6. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 6. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 6. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 6. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence of SEQ ID NO: 6.

[0240] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60% identical to SEQ ID NO: 7. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 70% identical to SEQ ID NO: 7. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 80% identical to SEQ ID NO: 7. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 7. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 7. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 7. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 7. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 7. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 7. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 7. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence of SEQ ID NO: 7.

[0241] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60% identical to SEQ ID NO: 8. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 70% identical to SEQ ID NO: 8. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 80% identical to SEQ ID NO: 8. In someATTORNEY DOCKET NO. VRD-021BWO1 embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 8. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 8. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 8. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 8. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 8. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 8. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 8. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence of SEQ ID NO: 8.

[0242] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60% identical to SEQ ID NO: 9. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 70% identical to SEQ ID NO: 9. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 80% identical to SEQ ID NO: 9. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 9. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 9. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 9. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 9. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 9. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 9. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 9. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence of SEQ ID NO: 9.

[0243] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60% identical to SEQ ID NO: 10. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 70% identical to SEQ ID NO: 10. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 80% identical to SEQ ID NO: 10. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85%ATTORNEY DOCKET NO. VRD-021BWO1 identical to SEQ ID NO: 10. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 10. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 10. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 10. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 10. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 10. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 10. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence of SEQ ID NO: 10.

[0244] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 60% identical to SEQ ID NO: 11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 70% identical to SEQ ID NO: 11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 80% identical to SEQ ID NO: 11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 96% identical to SEQ ID NO: 11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 98% identical to SEQ ID NO: 11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 11. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence of SEQ ID NO: 11.

[0245] In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3. The CDR1, CDR2, and CDR3 can be defined by any numbering convention commonly known in the art (e.g., Chothia, North, IMGT, Kabat). In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 as defined in any one of SEQ ID NOs: 1-11.

[0246] In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 as defined in SEQ ID NO: 1. In some embodiments, the anti-HSA sdAb comprises a CDR1,ATTORNEY DOCKET NO. VRD-021BWO1CDR2, and CDR3 as defined in SEQ ID NO: 2. In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 as defined in SEQ ID NO: 3. In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 as defined in SEQ ID NO: 4. In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 as defined in SEQ ID NO: 5.

[0247] In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 as defined in SEQ ID NO: 6. In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 as defined in SEQ ID NO: 7. In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 as defined in SEQ ID NO: 8. In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 as defined in SEQ ID NO: 9. In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 as defined in SEQ ID NO: 10. In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 as defined in SEQ ID NO: 11.

[0248] In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 as defined in Table A2.Table A2. Exemplary amino acid sequences of anti-HSA sdAbs. The CDRs, as defined by different numbering conventions, are in bold.ATTORNEY DOCKET NO. VRD-021BWO1ATTORNEY DOCKET NO. VRD-021BWO1ATTORNEY DOCKET NO. VRD-021BWO1

[0249] It is contemplated that a sdAb provided by the present invention may consist of an VHH described herein. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 1. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 2. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 3. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 4. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 5. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 6. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 7. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 8. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 9. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 10. In some embodiments, the sdAb consists of an amino acid sequence of SEQ ID NO: 11.

[0250] In some embodiments, the anti-HSA sdAb comprises a CDR1, CDR2, and CDR3 comprising sequences selected from Table Bl, Table B2, Table B3, and / or Table B4.Table Bl. Kabat CDR Sequences of Exemplary anti-HSA sdAbs.Table B2. North CDR Sequences of Exemplary anti-HSA sdAbs.ATTORNEY DOCKET NO. VRD-021BWO1Table B3. IMGT CDR Sequences of Exemplary anti-HSA sdAbs.Table B4. Chothia CDR Sequences of Exemplary anti-HSA sdAbs.

[0251] In some embodiments, the anti-HSA 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 moreATTORNEY DOCKET NO. VRD-021BWO1 than 2 amino acid residues from GQSTSR (SEQ ID NO: 101). In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0252] In some embodiments, the anti-HSA 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 than 2 amino acid residues from GRSASR (SEQ ID NO: 102). In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA sdAb comprises a CDR1 comprising an amino acid sequence of SFGMS (SEQ ID NO: 91), a CDR2 comprising an amino acidATTORNEY DOCKET NO. VRD-021BWO1 sequence of AIDSGGADTRYAESVKG (SEQ ID NO: 96), and a CDR3 comprising an amino acid sequence of GRSASR (SEQ ID NO: 102).

[0253] In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0254] In some embodiments, the anti-HSA 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 anti-HSA 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:ATTORNEY DOCKET NO. VRD-021BWO1103). In some embodiments, the anti-HSA 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 anti-HSA 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).

[0255] In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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 ID NO: 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 anti-HSA 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).

[0256] In some embodiments, the anti-HSA 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 IDATTORNEY DOCKET NO. VRD-021BWO1NO: 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0257] In some embodiments, the anti-HSA 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 anti-HSA 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 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 anti-HSA 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 anti-HSA sdAb comprises a CDR1 comprising an aminoATTORNEY DOCKET NO. VRD-021BWO1 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).

[0258] In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0259] In some embodiments, the anti-HSA 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 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 anti-HSA 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 thatATTORNEY DOCKET NO. VRD-021BWO1 differs by no more than 2 amino acid residues from TIGQSTSR (SEQ ID NO: 115). In some embodiments, the anti-HSA 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 anti-HSA 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).

[0260] In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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 anti-HSA sdAb comprises a CDR1 comprising an amino acid sequence of AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence of AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence of TIGRSASR (SEQ ID NO: 116).

[0261] In some embodiments, the anti-HSA 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 CDR3ATTORNEY DOCKET NO. VRD-021BWO1 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0262] In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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 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 anti-HSA sdAbATTORNEY DOCKET NO. VRD-021BWO1 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).

[0263] In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0264] In some embodiments, the anti-HSA 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, the anti-HSA 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 thatATTORNEY DOCKET NO. VRD-021BWO1 differs by no more than 2 amino acid residues from TIGRSTSR (SEQ ID NO: 118). In some embodiments, the anti-HSA 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 anti-HSA 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).

[0265] In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0266] In some embodiments, the anti-HSA 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 isATTORNEY DOCKET NO. VRD-021BWO1 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0267] In some embodiments, the anti-HSA 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 anti- HSA 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 anti-HSA 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, theATTORNEY DOCKET NO. VRD-021BWO1 anti-HSA 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).

[0268] In some embodiments, the anti-HSA 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 anti- HSA 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 anti-HSA 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 anti-HSA 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).

[0269] In some embodiments, the anti-HSA 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 anti-HSA 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 ISSDGSGT (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). InATTORNEY DOCKET NO. VRD-021BWO1 some embodiments, the anti-HSA 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 anti-HSA 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).

[0270] In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0271] In some embodiments, the anti-HSA 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 ISSDSSGT (SEQ ID NO:ATTORNEY DOCKET NO. VRD-021BWO1127), 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0272] In some embodiments, the anti-HSA 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 anti- HSA 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 anti-HSA 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 amino acid residue from TIGRSTSR (SEQ ID NO: 118). In some embodiments, the anti-HSA sdAb comprises a CDR1 comprising an amino acid sequence of GFSFGSFG (SEQATTORNEY DOCKET NO. VRD-021BWO1ID 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).

[0273] In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0274] In some embodiments, the anti-HSA 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 anti- HSA 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 anti-HSA sdAb comprises a CDR1 comprising an amino acid sequence that differs by noATTORNEY DOCKET NO. VRD-021BWO1 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 anti-HSA 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).

[0275] In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0276] In some embodiments, the anti-HSA 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 amino acid residues from GRSASR (SEQ ID NO: 102). In some embodiments, the anti-HSA sdAb comprises a CDR1 comprising an amino acid sequence that differs by no more than 2ATTORNEY DOCKET NO. VRD-021BWO1 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 anti-HSA 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 anti-HSA 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).

[0277] In some embodiments, the anti-HSA 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: 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 anti- HSA 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: 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 anti- HSA 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: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 anti-HSA sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence of SSDGSG (SEQ ID NO: 134), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0278] In some embodiments, the anti-HSA 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-021BWO1GFTFGQF (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 (SEQ ID NO: 135), 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 anti- HSA 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 (SEQ ID NO: 135), 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 anti- HSA 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 (SEQ ID NO:135), 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 anti-HSA sdAb comprises a CDR1 comprising an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence of SSDASG (SEQ ID NO: 135), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103).

[0279] In some embodiments, the anti-HSA 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 anti- HSA 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 anti- HSA 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 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 anti-HSA sdAbATTORNEY DOCKET NO. VRD-021BWO1 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).

[0280] In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0281] In some embodiments, the anti-HSA 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 anti-HSA 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 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 anti-HSA sdAbATTORNEY DOCKET NO. VRD-021BWO1 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 anti-HSA 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).

[0282] In some embodiments, the anti-HSA 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 anti-HSA 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 anti-HSA 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 anti-HSA 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).

[0283] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acidATTORNEY DOCKET NO. VRD-021BWO1 sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101.

[0284] In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 1 with no more than 5 amino acid changes as compared to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 1 with no more than 4 amino acid changes as compared to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 1 with no more than 3 amino acid changes as compared to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 1 with no more than 2 amino acid changes as compared to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 1 with no more than 1 amino acid change as compared to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101.ATTORNEY DOCKET NO. VRD-021BWO1

[0285] In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 85% identical to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti- HSA sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101.

[0286] In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 1 with no more than 5 amino acid changes as compared to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 1 with no more than 4 amino acid changes as compared to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 1 with no more than 3 amino acid changes as compared to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 1 with no more than 2 amino acid changes as compared to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and theATTORNEY DOCKET NO. VRD-021BWO1CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 1 with no more than 1 amino acid change as compared to SEQ ID NO: 1, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101.

[0287] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101.

[0288] In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 2 with no more than 5 amino acid changes as compared to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 2 with no more than 4 amino acid changes as compared to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 2 with no more than 3 amino acid changes as compared to SEQ ID NO: 2, provided that theATTORNEY DOCKET NO. VRD-021BWO1CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 2 with no more than 2 amino acid changes as compared to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 2 with no more than 1 amino acid change as compared to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101.

[0289] In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 85% identical to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti- HSA sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101.

[0290] In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 2 with no more than 5 amino acid changes as compared to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO:ATTORNEY DOCKET NO. VRD-021BWO1101. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 2 with no more than 4 amino acid changes as compared to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 2 with no more than 3 amino acid changes as compared to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 2 with no more than 2 amino acid changes as compared to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 2 with no more than 1 amino acid change as compared to SEQ ID NO: 2, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101.

[0291] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence ofATTORNEY DOCKET NO. VRD-021BWO1SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101.

[0292] In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 3 with no more than 5 amino acid changes as compared to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 3 with no more than 4 amino acid changes as compared to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 3 with no more than 3 amino acid changes as compared to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 3 with no more than 2 amino acid changes as compared to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 3 with no more than 1 amino acid change as compared to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101.

[0293] In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 85% identical to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acidATTORNEY DOCKET NO. VRD-021BWO1 sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti- HSA sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101.

[0294] In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 3 with no more than 5 amino acid changes as compared to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 3 with no more than 4 amino acid changes as compared to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 3 with no more than 3 amino acid changes as compared to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 3 with no more than 2 amino acid changes as compared to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 3 with no more than 1 amino acid change as compared to SEQ ID NO: 3, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 95, and the CDR3 has the amino acid sequence of SEQ ID NO: 101.

[0295] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 4, provided that theATTORNEY DOCKET NO. VRD-021BWO1CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102.

[0296] In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 4 with no more than 5 amino acid changes as compared to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 4 with no more than 4 amino acid changes as compared to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 4 with no more than 3 amino acid changes as compared to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 4 with no more than 2 amino acid changes as compared to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 4 with no more than 1 amino acid change as compared to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acidATTORNEY DOCKET NO. VRD-021BWO1 sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102.

[0297] In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 85% identical to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 95% identical to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 97% identical to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti- HSA sdAb has an amino acid sequence at least 99% identical to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102.

[0298] In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 4 with no more than 5 amino acid changes as compared to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 4 with no more than 4 amino acid changes as compared to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 4 with no more than 3 amino acid changes as compared to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 4 with no more than 2 amino acidATTORNEY DOCKET NO. VRD-021BWO1 changes as compared to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-HSA sdAb has a variant sequence of SEQ ID NO: 4 with no more than 1 amino acid change as compared to SEQ ID NO: 4, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 91, the CDR2 has the amino acid sequence of SEQ ID NO: 96, and the CDR3 has the amino acid sequence of SEQ ID NO: 102.

[0299] In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 85% identical to SEQ ID NO: 5, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 92, the CDR2 has the amino acid sequence of SEQ ID NO: 97, and the CDR3 has the amino acid sequence of SEQ ID NO: 103. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 90% identical to SEQ ID NO: 5, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 92, the CDR2 has the amino acid sequence of SEQ ID NO: 97, and the CDR3 has the amino acid sequence of SEQ ID NO: 103. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 95% identical to SEQ ID NO: 5, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 92, the CDR2 has the amino acid sequence of SEQ ID NO: 97, and the CDR3 has the amino acid sequence of SEQ ID NO: 103. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 97% identical to SEQ ID NO: 5, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 92, the CDR2 has the amino acid sequence of SEQ ID NO: 97, and the CDR3 has the amino acid sequence of SEQ ID NO: 103. In some embodiments, the anti-HSA sdAb comprises an amino acid sequence at least 99% identical to SEQ ID NO: 5, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 92, the CDR2 has the amino acid sequence of SEQ ID NO: 97, and the CDR3 has the amino acid sequence of SEQ ID NO: 103.

[0300] In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 5 with no more than 5 amino acid changes as compared to SEQ ID NO: 5, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 92, the CDR2 has the amino acid sequence of SEQ ID NO: 97, and the CDR3 has the amino acid sequence of SEQ ID NO: 103. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 5 with no more than 4 amino acid changes as compared to SEQ ID NO: 5, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 92, the CDR2 has the amino acid sequence of SEQ ID NO: 97, and the CDR3 has the amino acid sequence of SEQ ID NO:ATTORNEY DOCKET NO. VRD-021BWO1103. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 5 with no more than 3 amino acid changes as compared to SEQ ID NO: 5, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 92, the CDR2 has the amino acid sequence of SEQ ID NO: 97, and the CDR3 has the amino acid sequence of SEQ ID NO: 103. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 5 with no more than 2 amino acid changes as compared to SEQ ID NO: 5, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 92, the CDR2 has the amino acid sequence of SEQ ID NO: 97, and the CDR3 has the amino acid sequence of SEQ ID NO: 103. In some embodiments, the anti-HSA sdAb comprises a variant sequence of SEQ ID NO: 5 with no more than 1 amino acid change as compared to SEQ ID NO: 5, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 92, the CDR2 has the amino acid sequence of SEQ ID NO: 97, and the CDR3 has the amino acid sequence of SEQ ID NO: 103.

[0301] In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 85% identical to SEQ ID NO: 5, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 92, the CDR2 has the amino acid sequence of SEQ ID NO: 97, and the CDR3 has the amino acid sequence of SEQ ID NO: 103. In some embodiments, the anti-HSA sdAb has an amino acid sequence at least 90% identical to SEQ ID NO: 5, provided that the CDR1 has the amino acid sequence of SEQ ID NO: 92, the CDR2 has the amino acid sequence of SEQ ID NO: 97, and the CDR3 ha...

Claims

1. ATTORNEY DOCKET NO. VRD-021BWO1CLAIMSWhat is claimed is:

1. A fusion protein comprising an Fc region fused to a single domain antibody (sdAb) that binds to human serum albumin (HS A), wherein the Fc region comprises amino acid substitutions at positions: a. 252, 254, 256, 309, 311, 428, 433, and / or 434; b. 252, 254, 256, 433, and / or 434; c. 252, 254, 256, 428, 433, and / or 434; or d. 252, 254, 256, 428, and / or 434; wherein the positions are numbered according to the EU index; and wherein the sdAb comprises: e. 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); f. 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); g. 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); h. 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); i. 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);ATTORNEY DOCKET NO. VRD-021BWO1 j. 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); k. 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); l. 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); m. 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); n. a CDR1 comprising an amino acid sequence of AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence of AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence of TIGRSASR (SEQ ID NO: 116); o. 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 of TIGSSTTPSG (SEQ ID NO: 117); p. 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); q. 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);ATTORNEY DOCKET NO. VRD-021BWO1 r. 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); s. 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); t. 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); u. 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); v. 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); w. 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); x. 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); y. 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);ATTORNEY DOCKET NO. VRD-021BWO1 z. 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); aa. 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); bb. 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); cc. 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); dd. 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); ee. a CDR1 comprising an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence of SSDGSG (SEQ ID NO:134), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103); ff a CDR1 comprising an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence of SSDASG (SEQ ID NO:135), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103); gg. 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);ATTORNEY DOCKET NO. VRD-021BWO1 hh. 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); ii. 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); or jj. 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).

2. The fusion protein of claim 1, wherein the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 1-11.

3. The fusion protein of any one of the preceding claims, wherein the sdAb comprises an amino acid sequence of any one of SEQ ID NOs: 1-11.

4. The fusion protein of any one of the preceding claims, wherein the sdAb, when produced in a recombinant cell, has a yield of at least 400 mg / mL.

5. The fusion protein of any one of the preceding claims, wherein the sdAb has a wavelength shift of 1 nm or less according to affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS).

6. The fusion protein of any one of the preceding claims, wherein the sdAb has a DNA score of less than 3 according to a polyreactive ELISA.

7. The fusion protein of any one of the preceding claims, wherein the sdAb has a Tmof at least 55°C.ATTORNEY DOCKET NO. VRD-021BWO18. The fusion protein of any one of the preceding claims, wherein the sdAb has a Tagg266 of at least 60°C.

9. The fusion protein of any one of the preceding claims, wherein the sdAb has a Tagg266 of at least 65°C.

10. The fusion protein of any one of the preceding claims, wherein the sdAb is fused to the C-terminus of the Fc region.

11. The fusion protein of any one of claims 1-9, wherein the sdAb is fused to the N- terminus of the Fc region.

12. The fusion protein of any one of the preceding claims, wherein the Fc region comprises amino acid substitutions at positions: a. 252, 254, 256, 433, and 434; b. 252, 254, 256, 428, 433, and 434; or c. 252, 254, 256, 428, and 434; wherein the positions are numbered according to the EU index.

13. The fusion protein of any one of the preceding claims, wherein the Fc region comprises amino acid substitutions of: a. 252Y, 254T, 256E, 433K, and / or 434F; b. 252Y, 254T, 256E, 433K, and / or 434Y; c. 252Y, 254T, 256E, 433R, and / or 434Y; d. 252Y, 254T, 256E, 433R, and / or 434F; e. 252Y, 254T, 256E, 428L, 433K, and / or 434F; f. 252Y, 254T, 256E, 428L, 433K, and / or 434Y; g. 252Y, 254T, 256E, 428L, 433R, and / or 434F; or h. 252Y, 254T, 256E, 428L, and / or 434F; wherein the positions are numbered according to the EU index.

14. The fusion protein of any one of the preceding claims, wherein the Fc region comprises amino acid substitutions of:ATTORNEY DOCKET NO. VRD-021BWO1 a. 252Y, 254T, 256E, 433K, and 434F; b. 252Y, 254T, 256E, 433K, and 434Y; c. 252Y, 254T, 256E, 433R, and 434Y; d. 252Y, 254T, 256E, 433R, and 434F; e. 252Y, 254T, 256E, 428L, 433K, and 434F; f. 252Y, 254T, 256E, 428L, 433K, and 434Y; g. 252Y, 254T, 256E, 428L, 433R, and 434F; or h. 252Y, 254T, 256E, 428L, and 434F; wherein the positions are numbered according to the EU index.

15. A fusion protein comprising an Fc region fused to an sdAb that binds to HSA, wherein a. the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F; and b. the sdAb comprises: i. 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); ii. 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); iii. 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); iv. 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); v. a CDR1 comprising an amino acid sequence of QFGMS (SEQ ID NO: 92), a CDR2 comprising an amino acid sequence ofATTORNEY DOCKET NO. VRD-021BWO1AISSDSSGTIYADSVKG (SEQ ID NO: 99), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103); vi. 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); vii. 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); or viii. 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).

16. A fusion protein comprising an Fc region fused to an sdAb that binds to HSA, wherein a. the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434 Y; and b. the sdAb comprises: i. 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); ii. 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); iii. 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-021BWO1 iv. 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); v. 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); vi. 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); vii. 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); or viii. 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).

17. A fusion protein comprising an Fc region fused to an sdAb that binds to HSA, wherein a. the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F; and b. the sdAb comprises i. 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); ii. a CDR1 comprising an amino acid sequence of AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence ofATTORNEY DOCKET NO. VRD-021BWO1AIDSGGTDTR (SEQ ID NO: 110), and a CDR3 comprising an amino acid sequence of TIGQSTSR (SEQ ID NO: 115); iii. 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); or iv. 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).

18. A fusion protein comprising an Fc region fused to an sdAb that binds to HSA, wherein a. the Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434 Y; and b. the sdAb comprises i. 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); ii. 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); iii. 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); or iv. 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).ATTORNEY DOCKET NO. VRD-021BWO119. The fusion protein of any one of claims 15-18, wherein the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1.

20. The fusion protein of any one of claims 15-19, wherein the sdAb comprises an amino acid sequence of SEQ ID NO: 1.

21. The fusion protein of any one of the preceding claims, 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: 13-38.

22. The fusion protein of any one of the preceding claims, wherein the Fc region comprises an amino acid sequence of any one of SEQ ID NOs: 13-38.

23. The fusion protein of any one of the preceding claims, wherein the fusion protein further comprises a linker between the sdAb and the Fc region.

24. The fusion protein of claim 23, wherein the linker comprises glycine and serine.

25. The fusion protein of claim 23 or 24, wherein the linker comprises one or more repeating units of GGGGS.

26. The fusion protein of any one of claims 23-25, 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.

27. The fusion protein of any one of claims 23-25, wherein the linker comprises 6 repeating units of GGGGS.

28. The fusion protein of any one of claims 23-25, wherein the linker comprises 8 repeating units of GGGGS.ATTORNEY DOCKET NO. VRD-021BWO129. The fusion protein of any one of claims 23-28, wherein the fusion protein comprises, from N-terminal to C-terminal, the Fc region, the linker, and the sdAb.

30. The fusion protein of any one of claims 23-28, wherein the fusion protein comprises, from N-terminal to C-terminal, the sdAb, the linker, and the Fc region.

31. The fusion protein of any one of the preceding claims, wherein the Fc region further comprises knob-in-to-hole mutations.

32. The fusion protein of claim 31, wherein the knob-in-to-hole mutations comprise: a. Y349C, T366S, L368A, and Y407V; b. S354C and T366W; c. T366S, L368A, and Y407V; or d. T366W.

33. The fusion protein of any one of the preceding claims, wherein the fusion protein comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 43-67 or 70-90.

34. The fusion protein of any one of the preceding claims, wherein the fusion protein comprises an amino acid sequence of any one of SEQ ID NOs: 43-67 or 70-90.

35. The fusion protein of any one of the preceding claims, wherein the fusion protein comprises an amino acid sequence of SEQ ID NO: 55.

36. The fusion protein of any one of claims 1-34, wherein the fusion protein comprises an amino acid sequence of SEQ ID NO: 56.

37. The fusion protein of any one of claims 1-34, wherein the fusion protein comprises an amino acid sequence of SEQ ID NO: 58.

38. The fusion protein of any one of claims 1-34, wherein the fusion protein comprises an amino acid sequence of SEQ ID NO: 59.ATTORNEY DOCKET NO. VRD-021BWO139. The fusion protein of any one of the preceding claims, wherein the fusion protein forms a heterodimer.

40. The fusion protein of claim 39, wherein the fusion protein forms a heterodimer with a second Fc region.

41. The fusion protein of claim 40, wherein the first Fc region further comprises a knob mutation, and the second Fc region further comprises a hole mutation.

42. The fusion protein of claim 40, wherein the second Fc region further comprises a knob mutation, and the first Fc region further comprises a hole mutation.

43. The fusion protein of claim 41 or 42, wherein the knob mutation comprises one or more amino acid substitutions of: a. S354C and T366W; or b. T366W.

44. The fusion protein of any one of claims 41-43, wherein the hole mutation comprises one or more amino acid substitutions of: a. Y349C, T366S, L368A, and Y407V; or b. T366S, L368A, and Y407V.

45. The fusion protein of any one of claims 40-44, wherein 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: 13-38.

46. The fusion protein of claim 45, wherein the second Fc region comprises an amino acid sequence selected from SEQ ID NOs: 13-38.

47. The fusion protein of any one of claims 1-38, wherein the fusion protein forms a homodimer.

48. A fusion protein comprising a first Fc region fused to an sdAb that binds to HSA, whereinATTORNEY DOCKET NO. VRD-021BWO1 a. the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y; and b. the sdAb comprises: i. 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); ii. 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); iii. 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); or iv. 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); wherein the fusion protein forms a heterodimer with a second Fc region, and wherein the second Fc region comprises an amino acid sequence selected from SEQ ID NOs: 13-38.

49. The fusion protein of claim 48, wherein the first Fc region further comprises amino acid substitutions of Y349C, T366S, L368A, and Y407V.

50. The fusion protein of claim 48 or 49, wherein the second Fc region comprises an amino acid sequence of SEQ ID NO: 19.

51. The fusion protein of any one of the preceding claims, wherein the fusion protein binds to HSA with a lower KD at pH 6.0 as compared to a KD at pH 7.4.ATTORNEY DOCKET NO. VRD-021BWO152. The fusion protein of any one of the preceding claims, wherein the fusion protein binds to HSA with a KD of less than 500 nM at pH 6.0.

53. The fusion protein of any one of the preceding claims, wherein the fusion protein binds to HSA with a KD of less than 1000 nM at pH 7.4.

54. The fusion protein of any one of the preceding claims, wherein the fusion protein binds to HSA with a KD of -200 nM.

55. The fusion protein of any one of the preceding claims, wherein the fusion protein blocks IgGs from binding to FcRn.

56. The fusion protein of any one of the preceding claims, wherein the fusion protein blocks or reduces naturally occurring recycling of IgGs.

57. The fusion protein of claim 55 or 56, wherein the fusion protein results in increased catabolism of the IgGs.

58. The fusion protein of any one of claims 55-57, wherein the IgGs comprise pathogenic autoantibodies.

59. A molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, wherein the first Fc region and / or the second Fc region comprises amino acid substitutions at positions: a. 252, 254, 256, 309, 311, 428, 433, and / or 434; b. 252, 254, 256, 433, and / or 434; c. 252, 254, 256, 428, 433, and / or 434; or d. 252, 254, 256, 428, and / or 434; and wherein the sdAb comprises: e. 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);ATTORNEY DOCKET NO. VRD-021BWO1 f. 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); g. 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); h. 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); i. 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); j. 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); k. 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); l. 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); m. 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);ATTORNEY DOCKET NO. VRD-021BWO1 n. a CDR1 comprising an amino acid sequence of AASGFTFGSFGMS (SEQ ID NO: 105), a CDR2 comprising an amino acid sequence of AIDSGGADTR (SEQ ID NO: 111), and a CDR3 comprising an amino acid sequence of TIGRSASR (SEQ ID NO: 116); o. 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 of TIGSSTTPSG (SEQ ID NO: 117); p. 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); q. 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); r. 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); s. 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); t. 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); u. 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);ATTORNEY DOCKET NO. VRD-021BWO1 v. 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); w. 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); x. 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); y. 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); z. 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); aa. 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); bb. 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); cc. 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);ATTORNEY DOCKET NO. VRD-021BWO1 dd. 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); ee. a CDR1 comprising an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence of SSDGSG (SEQ ID NO:134), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103); ff a CDR1 comprising an amino acid sequence of GFTFGQF (SEQ ID NO: 129), a CDR2 comprising an amino acid sequence of SSDASG (SEQ ID NO:135), and a CDR3 comprising an amino acid sequence of GSSTTPSG (SEQ ID NO: 103); gg. 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); hh. 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); ii. 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); or jj. 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).

60. The molecule of protein of claim 59, wherein the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 1-11.ATTORNEY DOCKET NO. VRD-021BWO161. The molecule of claim 59 or 60, wherein the sdAb comprises an amino acid sequence of any one of SEQ ID NOs: 1-11.

62. The molecule of any one of claims 59-61, wherein the sdAb is fused to the C-terminus of the first Fc region.

63. The molecule of any one of claims 59-62, wherein the sdAb is fused to the N- terminus of the first Fc region.

64. The molecule of any one of claims 59-63, wherein the first Fc region comprises amino acid substitutions at positions a. 252, 254, 256, 433, and 434; b. 252, 254, 256, 428, 433, and 434; or c. 252, 254, 256, 428, and 434; wherein the positions are numbered according to the EU index.

65. The molecule of any one of claims 59-64, wherein the first Fc region comprises amino acid substitutions of: a. 252Y, 254T, 256E, 433K, and / or 434F; b. 252Y, 254T, 256E, 433K, and / or 434Y; c. 252Y, 254T, 256E, 433R, and / or 434Y; d. 252Y, 254T, 256E, 433R, and / or 434F; e. 252Y, 254T, 256E, 428L, 433K, and / or 434F; f. 252Y, 254T, 256E, 428L, 433K, and / or 434Y; g. 252Y, 254T, 256E, 428L, 433R, and / or 434F; or h. 252Y, 254T, 256E, 428L, and / or 434F; wherein the positions are numbered according to the EU index.

66. The molecule of any one of claims 59-65, wherein the first Fc region comprises amino acid substitutions of: a. 252Y, 254T, 256E, 433K, and 434F; b. 252Y, 254T, 256E, 433K, and 434Y; c. 252Y, 254T, 256E, 433R, and 434Y;ATTORNEY DOCKET NO. VRD-021BWO1 d. 252Y, 254T, 256E, 433R, and 434F; e. 252Y, 254T, 256E, 428L, 433K, and 434F; f. 252Y, 254T, 256E, 428L, 433K, and 434Y; g. 252Y, 254T, 256E, 428L, 433R, and 434F; or h. 252Y, 254T, 256E, 428L, and 434F; wherein the positions are numbered according to the EU index.

67. A molecule comprising: a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein a. the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F; and b. the sdAb comprises: i. 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); ii. 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); iii. 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); iv. 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); v. 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);ATTORNEY DOCKET NO. VRD-021BWO1 vi. 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); vii. 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); or viii. 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.

68. A molecule comprising: a first polypeptide comprising an Fc region fused to an sdAb that binds to HSA, wherein a. the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y; and b. the sdAb comprises: i. 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); ii. 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); iii. 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-021BWO1 iv. 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); v. 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); vi. 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); vii. 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); or viii. 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); 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.

69. A molecule comprising: a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein a. The first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F; and b. the sdAb comprises: i. 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);ATTORNEY DOCKET NO. VRD-021BWO1 ii. 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); iii. 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); or iv. 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); and a second polypeptide comprising a second Fc region, wherein the second Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 428L, 433K, and 434F.

70. A molecule comprising: a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein a. the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y; and b. the sdAb comprises: i. 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); ii. 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); iii. 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); orATTORNEY DOCKET NO. VRD-021BWO1 iv. 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); 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.

71. The molecule of any one of claims 59-70, wherein the sdAb comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1.

72. The molecule of claim 71, wherein the sdAb comprises an amino acid sequence of SEQ ID NO: 1.

73. The molecule of any one of claims 59-72, 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: 13-38.

74. The molecule of any one of claims 59-73, wherein the first Fc region comprises an amino acid sequence of any one of SEQ ID NOs: 13-38.

75. The molecule of any one of claims 59-74, wherein the first polypeptide further comprises a linker between the sdAb and the first Fc region.

76. The molecule of claim 75, wherein the linker comprises glycine and serine.

77. The molecule of claim 75 or 76, wherein the linker comprises one or more repeating units of GGGGS.

78. The molecule of any one of claims 75-77, 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.ATTORNEY DOCKET NO. VRD-021BWO179. The molecule of any one of claims 75-78, wherein the linker comprises 6 repeating units of GGGGS.

80. The molecule of any one of claims 75-78, wherein the linker comprises 8 repeating units of GGGGS.

81. The molecule of any one of claims 75-80, wherein the first polypeptide comprises, from N-terminal to C-terminal, the first Fc region, the linker, and the sdAb.

82. The molecule of any one of claims 75-80, wherein the first polypeptide comprises, from N-terminal to C-terminal, the sdAb, the linker, and the first Fc region.

83. The molecule of any one of claims 59-82, wherein the first Fc region further comprises knob-in-to-hole mutations.

84. The molecule of claim 59-83, wherein the knob-in-to-hole mutations comprise a. Y349C, T366S, L368A, and Y407V; b. S354C and T366W; c. T366S, L368A, and Y407V; or d. T366W.

85. The molecule of any one of claims 59-84, wherein the first polypeptide comprises an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 43-67 or 70-90.

86. The molecule of any one of claims 59-85, wherein the first polypeptide comprises an amino acid sequence of any one of SEQ ID NOs: 43-67 or 70-90.

87. The molecule of any one of claims 59-86, wherein the first polypeptide comprises an amino acid sequence of SEQ ID NO: 55.

88. The molecule of any one of claims 59-86, wherein the first polypeptide comprises an amino acid sequence of SEQ ID NO: 56.ATTORNEY DOCKET NO. VRD-021BWO189. The molecule of any one of claims 59-86, wherein the first polypeptide comprises an amino acid sequence of SEQ ID NO: 58.

90. The molecule of any one of claims 59-86, wherein the first polypeptide comprises an amino acid sequence of SEQ ID NO: 59.

91. The molecule of any one of claims 59-90, wherein the first polypeptide and the second polypeptide form a heterodimer.

92. The molecule of claim 91, wherein the first Fc region forms a heterodimer with the second Fc region.

93. The molecule of claim 92, wherein the first Fc region further comprises a knob mutation, and the second Fc region further comprises a hole mutation.

94. The molecule of claim 92, wherein the second Fc region further comprises a knob mutation, and the first Fc region further comprises a hole mutation.

95. The molecule of claim 93 or 94, wherein the knob mutation comprises one or more amino acid substitutions of: a. S354C and T366W; or b. T366W.

96. The molecule of any one of claims 93-95, wherein the hole mutation comprises one or more amino acid substitutions of: a. Y349C, T366S, L368A, and Y407V; or b. T366S, L368A, and Y407V.

97. The molecule of any one of claims 59-96, wherein 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: 13-38.ATTORNEY DOCKET NO. VRD-021BWO198. The molecule of any one of claims 59-97, wherein the second Fc region comprises an amino acid sequence selected from SEQ ID NOs: 13-38.

99. The molecule of any one of claims 59-90, wherein the first polypeptide forms a homodimer.

100. A molecule comprising a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, wherein a. the first Fc region comprises amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y; and b. the sdAb comprises: i. 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); ii. 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); iii. 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); or iv. 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); and a second polypeptide comprising a second Fc region comprising amino acid substitutions of 252Y, 254T, 256E, 433K, and 434Y; wherein the first Fc region forms a heterodimer with a second Fc region.ATTORNEY DOCKET NO. VRD-021BWO1101. The molecule of claim 100, wherein the first Fc region further comprises amino acid substitutions of Y349C, T366S, L368A, and Y407V.

102. The molecule of claim 100 or 101, wherein the first Fc region comprises an amino acid sequence of SEQ ID NO: 18.

103. The molecule of any one of claims 100-102, wherein the second Fc region comprises an amino acid sequence of SEQ ID NO: 19.

104. The molecule of any one of claims 59-103, wherein the molecule binds to HSA with a lower KD at pH 6.0 as compared to a KD at pH 7.4.

105. The molecule of any one of claims 59-104, wherein the molecule binds to HSA with a KD of less than 500 nM at pH 6.0.

106. The molecule of any one of claims 59-105, wherein the molecule binds to HSA with a KD of less than 1000 nM at pH 7.4.

107. The molecule of any one of claims 59-106, wherein the molecule binds to HSA with a KD of -200 nM.

108. The molecule of any one of claims 59-107, wherein the molecule blocks IgGs from binding to FcRn.

109. The molecule of any one of claims 59-108, wherein the molecule blocks or reduces naturally occurring recycling of IgGs.

110. The molecule of claim 108 or 109, wherein the molecule results in increased catabolism of the IgGs.

111. The molecule of any one of claims 108-110, wherein the IgGs comprise pathogenic autoantibodies.

112. A molecule comprising:ATTORNEY DOCKET NO. VRD-021BWO1 a first polypeptide comprising a first Fc region fused to an sdAb that binds to HSA, and a second polypeptide comprising a second Fc region, 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.

113. A nucleic acid encoding the fusion protein of any one of claims 1-58, or the molecule of any one of claims 59-112.

114. A vector comprising the nucleic acid of claim 113.

115. A host cell comprising the nucleic acid of claim 113 or the vector of claim 114.

116. A pharmaceutical composition comprising the fusion protein of any one of claims 1-58, the molecule of any one of claims 59-112, the nucleic acid of claim 113, the vector of claim 114, or the host cell of claim 115, and a pharmaceutically acceptable carrier.

117. A method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of the fusion protein of any one of claims 1-58.

118. A method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of the molecule of any one of claims 59-112.

119. The method of any one of claims 117-118, wherein the disease or disorder is an autoimmune disease.

120. The method of any one of claims 117-119, 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),ATTORNEY DOCKET NO. VRD-021BWO1 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.

121. A method for treating a pathology associated with elevated levels of an IgG in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the fusion protein of any one of claims 1-58.

122. A method for treating a pathology associated with elevated levels of an IgG in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the molecule of any one of claims 59-112.

123. A method of reducing biological activity of an IgG in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the fusion protein of any one of claims 1-58.

124. A method of reducing biological activity of an IgG in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the molecule of any one of claims 59-112.

125. The method of claim 123 or 124, wherein the administration of the fusion protein or the molecule reduces IgG level to less than 50%, to less than 40%, to less than 30%, or to less than 25% for at least 5 days, 7 days, 10 days, 15 days, or 20 days post administration.

126. The method of any one of claims 121-125, wherein the subject has an autoimmune disease.

127. A method of producing a fusion protein comprising an Fc region fused to a single domain antibody (sdAb) that binds to human serum albumin (HSA), comprising introducing one or more amino acid additions, deletions, or substitutions to a reference sdAb, wherein the reference sdAb comprises:ATTORNEY DOCKET NO. VRD-021BWO1 a. 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); b. 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); c. 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); d. 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); e. 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); f. 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); g. 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); or h. 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).ATTORNEY DOCKET NO. VRD-021BWO1128. The method of claim 127, wherein the reference sdAb comprises an amino acid sequence of any one of SEQ ID NOs: 1-11.

129. The method of claim 127 or claim 128, wherein the method comprises introducing one or more amino acid additions at the C-terminus of the reference sdAb.

130. The method of claim 129, wherein the one or more amino acid additions is an addition of one or more alanine residues.

131. The method of any one of claims 127-130, wherein the method comprises introducing one or more amino acid substitutions in the CDRs and / or framework regions of the reference sdAb.

132. The method of claim 131, wherein the one or more amino acid substitutions comprises F32A and / or M34 A.

133. An Fc-sdAb fusion produced by the method of any one of claims 127-132.

134. The Fc-sdAb fusion of claim 133, wherein the sdAb comprises an amino acid sequence of any one of SEQ ID NOs: 9-11.

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