FCRN / antigen-binding molecule and method of use

Abstract

Binding molecules are provided herein that comprise a human neonatal Fc receptor (FcRn) binding molecule and at least one antigen binding domain linked to the FcRn binding molecule. Also provided herein are polynucleotides, vectors, host cells, and production methods. Further provided is a method of treating antibody-mediated disorders with an FcRn / antigen binding molecule.

Description

Technical Field

[0001] The present disclosure relates to the human neonatal Fc receptor (FcRn) / antigen-binding molecule and methods of using the same.

Background Art

[0002] Immunoglobulin gamma (IgG) antibodies play important roles in the pathology of many diseases, such as autoimmune diseases, inflammatory diseases, and disorders where the pathology is characterized by overexpression of IgG antibodies.

[0003] The half-life of IgG in serum is extended relative to the serum half-life of other plasma proteins, due in part to the binding of the Fc region of IgG to the Fc receptor FcRn. FcRn binds to IgG and protects IgG from transport to degradative lysosomes by recycling IgG to the extracellular compartment. This recycling is facilitated by the pH-dependent binding of IgG to FcRn, and the IgG / FcRn interaction is stronger at acidic endosomal pH than at extracellular physiological pH.

[0004] When the serum concentration of IgG reaches levels that exceed the available FcRn molecules, unbound IgG is not protected from lysosomal degradation and thus has a reduced serum half-life. Thus, inhibition of IgG binding to FcRn reduces the serum half-life of IgG by preventing endosomal recycling of IgG. Agents that antagonize the binding of IgG to FcRn, such as FcRn-binding molecules, are useful for modulating, treating, or preventing antibody-mediated disorders, such as autoimmune diseases or inflammatory diseases.

[0005] Efgartigimod is an engineered Fc of the za allotype derived from modified human immunoglobulin (Ig) gamma (IgG) 1 that binds to human FcRn with nanomolar affinity. Efgartigimod encompasses the IgG1 Fc region and has been engineered using ABDEG technology to increase its affinity for FcRn at both physiological and acidic pH. The increased affinity of efgartigimod for FcRn at both acidic and physiological pH results in blockade of FcRn-mediated recycling of IgG. Efgartigimod is approved in the United States and Japan as a weekly intravenous injection for use in the treatment of generalized myasthenia gravis and is being developed for the treatment of several other antibody-mediated disorders.

[0006] FcRn also binds to and recycles serum albumin, a regulator of serum cholesterol levels. Efgartigimod advantageously does not negatively impact serum albumin levels in human subjects. However, recently, it has been shown that anti-FcRn antibodies can cause a reduction in serum albumin levels and an accompanying increase in serum cholesterol levels in human subjects, both of which are undesirable.

[0007] Accordingly, there is a need in the art for improved agents for use in the treatment of antibody-mediated disorders that antagonize FcRn binding to IgG and have a longer half-life, lower dose, less frequent dosing, better maintenance of albumin levels, and / or reduced or eliminated FcRn degradation. SUMMARY OF THE INVENTION

[0008] Broadly, the present disclosure is directed to neonatal Fc receptor (FcRn) binding molecules (FcRn / antigen binding molecules) linked to one antigen binding domain and methods of using the same. Unexpectedly, it is shown for the first time in this application that including an antigen binding portion increases the stability and FcRn occupancy of the FcRn binding molecule.

[0009] In one aspect, provided herein is an FcRn / antigen-binding molecule comprising a variant IgG Fc region and only one antigen-binding domain linked to the variant IgG Fc region, wherein the antigen-binding domain specifically binds to a human antigen, the variant IgG Fc region comprises or consists of a first Fc domain and a second Fc domain that form a dimer, and the variant Fc region comprises one or more mutations of amino acid residues that form the interface of the CH3 domain of the Fc domain.

[0010] In some embodiments, the FcRn / antigen-binding molecule has a molecular weight of about 50 to about 140 kilodaltons (kDa). In some embodiments, the FcRn antagonist has a molecular weight of about 60 kDa to about 104 kDa. In some embodiments, the FcRn antagonist has a molecular weight of 60 kDa to 104 kDa. In some embodiments, the FcRn antagonist has a molecular weight of about 60 kDa. In some embodiments, the FcRn antagonist has a molecular weight of about 104 kDa. In some embodiments, the FcRn antagonist has a molecular weight of 60 kDa. In some embodiments, the FcRn antagonist has a molecular weight of 104 kDa.

[0011] In some embodiments, the FcRn-binding molecule is a variant Fc region, the variant Fc region comprises a first Fc domain and a second Fc domain that form a dimer, and at least one of the Fc domains comprises amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively.

[0012] In some embodiments, the variant Fc region consists of a first Fc domain and a second Fc domain that form a dimer.

[0013] In some embodiments, administration of a therapeutically effective amount of the FcRn / antigen-binding molecule to a subject results in a reduction of serum IgG in the subject. In some embodiments, administration of a therapeutically effective amount of the FcRn / antigen-binding molecule to a subject results in a reduction of serum IgG in the subject of at least about 55% compared to the baseline level of serum IgG in the subject.

[0014] In some embodiments, administration of a therapeutically effective amount of the FcRn / antigen-binding molecule to a subject does not reduce the FcRn level and / or albumin level in the subject.

[0015] In some embodiments, the clearance of the FcRn / antigen-binding molecule in a subject is less than about 0.2, about 0.19, about 0.18, about 0.17, about 0.16, about 0.15, about 0.14, about 0.13, about 0.12, about 0.11, about 0.1, about 0.09, about 0.08, about 0.07, about 0.06, or about 0.05 l / hour after a single administration of a therapeutically effective amount of the FcRn / antigen-binding molecule to the subject.

[0016] In some embodiments, the terminal half-life (t 1 / 2,z ) of the FcRn / antigen-binding molecule is greater than about 3, about 3.5, about 4, about 4.5, about 5, about 5.5, about 6, about 6.5, about 7, about 7.5, about 8, about 8.5, about 9, about 9.5, about 10, about 10.5, about 11, about 11.5, about 12, about 12.5, about 13, about 13.5, about 14, about 14.5, about 15, about 15.5, about 16, about 16.5, about 17, about 17.5, about 18, about 18.5, about 19, about 19.5, about 20, about 20.5, about 21, about 21.5, about 22, about 22.5, about 23, about 23.5, about 24, about 24.5, about 25, about 25.5, about 26, about 26.5, about 27, about 27.5, about 28, about 28.5, about 29, about 29.5, or about 30 days.

[0017] In some embodiments, the FcRn / antigen-binding molecule binds to FcRn at pH 5.5 and / or pH 6.0 and, optionally, binds with a higher affinity to FcRn at pH 5.5 and / or pH 6.0 than the affinity of efalizumab to FcRn as measured by surface plasmon resonance.

[0018] In some embodiments, the FcRn / antigen-binding molecule binds to FcRn at pH 5.5 and / or pH 6.0 and, optionally, binds with an affinity lower than the affinity of efalizumab to FcRn at pH 5.5 and / or pH 6.0 as measured by surface plasmon resonance.

[0019] In some embodiments, the variant Fc region comprises or consists of a first Fc domain and a second Fc domain that form a dimer, and the first Fc domain and / or the second Fc domain comprises the amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively. In some embodiments, the first Fc domain and / or the second Fc domain comprises the amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0020] In some embodiments, both the first Fc domain and the second Fc domain comprise the amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively. In some embodiments, both the first Fc domain and the second Fc domain comprise the amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0021] In some embodiments, the first Fc domain and / or the second Fc domain is an IgG1 Fc domain. In some embodiments, the first Fc domain and / or the second Fc domain is a human IgG Fc domain, such as a human IgG1 Fc domain.

[0022] In some embodiments, both the first Fc domain and the second Fc domain are IgG Fc domains, such as human IgG Fc domains. In some embodiments, both the first Fc domain and the second Fc domain are IgG1 Fc domains, such as human IgG1 Fc domains.

[0023] In some embodiments, the antigen-binding domain is fused to the C-terminus of the first Fc domain or the second Fc domain. In some embodiments, the N-terminus of the antigen-binding domain is fused to the C-terminus of the first Fc domain. In some embodiments, the N-terminus of the antigen-binding domain is fused to the C-terminus of the second Fc domain.

[0024] In some embodiments, the antigen-binding domain is fused to the N-terminus of the first Fc domain or the second Fc domain. In some embodiments, the N-terminus of the first Fc domain is fused to the C-terminus of the antigen-binding domain. In some embodiments, the N-terminus of the second Fc domain is fused to the C-terminus of the antigen-binding domain.

[0025] In some embodiments, the antigen-binding domain is fused to the first Fc domain or the second Fc domain via a linker. In some embodiments, the linker is a non-cleavable linker. In some embodiments, the linker is a peptide linker. In some embodiments, the peptide linker is a GS linker, optionally 8 to 40 amino acids in length, and optionally 20 or 30 amino acids in length.

[0026] In some embodiments, the antigen-binding domain is fused to the first Fc domain or the second Fc domain via an IgG hinge region or a portion thereof. In some embodiments, the first Fc domain contains amino acids E and D at EU positions 370 and 409, respectively, and the second Fc domain contains K at EU positions 357 and 399.

[0027] In some embodiments, the first Fc domain and / or the second Fc domain comprises an amino acid sequence independently selected from the amino acid sequences set forth in SEQ ID NO: 1, 2, or 3. In some embodiments, the first Fc domain and / or the second Fc domain comprises the amino acid sequence of SEQ ID NO: 2.

[0028] In some embodiments, both the first Fc domain and the second Fc domain comprise an amino acid sequence independently selected from the amino acid sequences set forth in SEQ ID NO: 1, 2, or 3. In some embodiments, both the first Fc domain and the second Fc domain comprise the amino acid sequence of SEQ ID NO: 2.

[0029] In some embodiments, the amino acid sequence of each of the first Fc domain and the second Fc domain consists of an amino acid sequence independently selected from the amino acid sequences set forth in SEQ ID NO: 1, 2, or 3. In some embodiments, the amino acid sequence of the first Fc domain or the amino acid sequence of the second Fc domain consists of SEQ ID NO: 2.

[0030] In some embodiments, the amino acid sequences of both the first Fc domain and the second Fc domain consist of SEQ ID NO: 2.

[0031] In some embodiments, the variant Fc region comprises one or more mutations of amino acid residues that form the interface of the CH3 domain of the Fc domain. In some embodiments, the variant Fc region comprises a knob-into-hole mutation.

[0032] In some embodiments, the amino acid sequence of the first Fc domain further comprises amino acid W at EU position 366.

[0033] In some embodiments, the amino acid sequence of the first Fc domain comprises an amino acid sequence selected from the amino acid sequences set forth in SEQ ID NO: 4, 5, or 6. In some embodiments, the amino acid sequence of the first Fc domain comprises the amino acid sequence of SEQ ID NO: 5.

[0034] In some embodiments, the amino acid sequence of the first Fc domain consists of an amino acid sequence selected from the amino acid sequences set forth in SEQ ID NO: 4, 5, or 6. In some embodiments, the amino acid sequence of the first Fc domain consists of the amino acid sequence of SEQ ID NO: 5.

[0035] In some embodiments, the amino acid sequence of the second Fc domain further comprises the amino acids S, A, and V at EU positions 366, 368, and 407, respectively.

[0036] In some embodiments, the amino acid sequence of the second Fc domain comprises an amino acid sequence selected from the amino acid sequences set forth in SEQ ID NO: 7, 8, or 9. In some embodiments, the amino acid sequence of the second Fc domain comprises the amino acid sequence of SEQ ID NO: 8.

[0037] In some embodiments, the amino acid sequence of the second Fc domain consists of an amino acid sequence selected from the amino acid sequences set forth in SEQ ID NO: 7, 8, or 9. In some embodiments, the amino acid sequence of the second Fc domain consists of the amino acid sequence of SEQ ID NO: 8.

[0038] In some embodiments, the antigen-binding domain is selected from a Fab domain, an sdAb, an scFv, and an antibody mimetic. In some embodiments, the antibody mimetic is an anticalin or a darpin. In some embodiments, the sdAb is a VHH domain.

[0039] In some embodiments, the antigen-binding domain specifically binds to a human antigen. In some embodiments, the human antigen is selected from IgE or HSA.

[0040] In some embodiments, the human antigen is IgE, the antigen-binding domain is a Fab fragment or scFv, and the Fab fragment or scFv comprises the HCDR1 amino acid sequence, HCDR2 amino acid sequence, and HCDR3 amino acid sequence of VH comprising the amino acid sequence of SEQ ID NO: 108, and the LCDR1 amino acid sequence, LCDR2 amino acid sequence, and LCDR3 amino acid sequence of VL comprising the amino acid sequence of SEQ ID NO: 107.

[0041] In some embodiments, the human antigen is IgE, the antigen-binding domain is a Fab domain or scFv domain, the Fab domain or scFv domain comprises a variable heavy chain domain (VH) and a variable light chain domain (VL), and VH and VL comprise CDR sequences selected from the group consisting of HCDR1 (SEQ ID NO: 101), HCDR2 (SEQ ID NO: 102), HCDR3 (SEQ ID NO: 103), LCDR1 (SEQ ID NO: 104), LCDR2 (SEQ ID NO: 105), and LCDR3 (SEQ ID NO: 106).

[0042] In some embodiments, VH comprises, or consists of, an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 108, and VL comprises, or consists of, an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 107. In some embodiments, VH comprises, or consists of, the amino acid sequence of SEQ ID NO: 108, and VL comprises, or consists of, the amino acid sequence of SEQ ID NO: 107.

[0043] In some embodiments, the human antigen is HSA, the antigen-binding domain is a VHH fragment, and the VHH fragment comprises the CDR1 amino acid sequence, CDR2 amino acid sequence, and CDR3 amino acid sequence of a VHH fragment comprising an amino acid sequence selected from SEQ ID NOs: 43-74, 84-90, and 120-127.

[0044] In some embodiments, the human antigen is HSA, the antigen-binding domain is a VHH domain, and the VHH domain is a) an amino acid sequence comprising SEQ ID NO: 13 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), b) an amino acid sequence comprising SEQ ID NO: 14 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), c) an amino acid sequence comprising SEQ ID NO: 15 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), d) an amino acid sequence comprising SEQ ID NO: 16 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), e) an amino acid sequence comprising SEQ ID NO: 17 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), f) an amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 18 (CDR2), and SEQ ID NO: 12 (CDR3), g) an amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 19 (CDR2), and SEQ ID NO: 12 (CDR3), h) an amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 20 (CDR2), and SEQ ID NO: 12 (CDR3), i) an amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 21 (CDR2), and SEQ ID NO: 12 (CDR3), j) an amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 22 (CDR2), and SEQ ID NO: 12 (CDR3), k) an amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 23 (CDR2), and SEQ ID NO: 12 (CDR3), l) an amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 24 (CDR2), and SEQ ID NO: 12 (CDR3), m) an amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 25 (CDR2), and SEQ ID NO: 12 (CDR3), n) an amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 26 (CDR2), and SEQ ID NO: 12 (CDR3), o) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 27 (CDR2), and SEQ ID NO: 12 (CDR3) p) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 28 (CDR2), and SEQ ID NO: 12 (CDR3) q) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 29 (CDR2), and SEQ ID NO: 12 (CDR3) r) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 30 (CDR2), and SEQ ID NO: 12 (CDR3) s) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 31 (CDR2), and SEQ ID NO: 12 (CDR3) t) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 32 (CDR2), and SEQ ID NO: 12 (CDR3) u) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 33 (CDR2), and SEQ ID NO: 12 (CDR3) v) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 34 (CDR3) w) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 35 (CDR3) x) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 36 (CDR3) y) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 37 (CDR3) z) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 38 (CDR3) aa) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 39 (CDR3) bb) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 40 (CDR3) cc) An amino acid sequence comprising SEQ ID NO: 15 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 36 (CDR3) dd) An amino acid sequence comprising SEQ ID NO: 15 (CDR1), SEQ ID NO: 21 (CDR2), and SEQ ID NO: 12 (CDR3), ee) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 41 (CDR2), and SEQ ID NO: 12 (CDR3), ff) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 20 (CDR2), and SEQ ID NO: 36 (CDR3), gg) An amino acid sequence comprising SEQ ID NO: 111 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), hh) An amino acid sequence comprising SEQ ID NO: 112 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), ii) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 113 (CDR2), and SEQ ID NO: 12 (CDR3), jj) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 114 (CDR2), and SEQ ID NO: 12 (CDR3), kk) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 115 (CDR3), ll) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 116 (CDR3), mm) An amino acid sequence comprising SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 117 (CDR3), nn) An amino acid sequence comprising SEQ ID NO: 118 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 119 (CDR3), oo) An amino acid sequence comprising SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 77 (CDR3), pp) An amino acid sequence comprising SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 78 (CDR3), qq) An amino acid sequence comprising SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 79 (CDR3), rr) An amino acid sequence comprising SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 80 (CDR3), (ss) An amino acid sequence comprising SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 81 (CDR3). (tt) An amino acid sequence comprising SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 82 (CDR3), and (uu) It comprises an amino acid sequence selected from the group consisting of amino acid sequences comprising SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 83 (CDR3).

[0045] In some embodiments, the antigen-binding domain is a VHH fragment, and the VHH fragment comprises an amino acid sequence comprising SEQ ID NO: 14 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3).

[0046] In some embodiments, the human antigen is HSA, the antigen-binding domain is a VHH domain, and the VHH domain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to an amino acid sequence selected from SEQ ID NOs: 43-74, 84-90, and 120-127. In some embodiments, the antigen-binding domain is a VHH domain, and the VHH domain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence set forth in SEQ ID NO: 44. In some embodiments, the antigen-binding domain comprises an amino acid sequence selected from SEQ ID NOs: 43-74, 84-90, and 120-127. In some embodiments, the antigen-binding domain comprises the amino acid sequence set forth in SEQ ID NO: 44.

[0047] In some embodiments, the FcRn / antigen-binding molecule further comprises one or more additional amino acids at the C-terminus of the antigen-binding domain, for example when the antigen-binding domain is a VHH fragment. In some embodiments, the one or more additional amino acids are selected from the group consisting of a) A, b) AG, c) GG, and d) PP. In some embodiments, the human antigen is HSA, the antigen-binding domain is a VHH domain, and the VHH domain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to an amino acid sequence selected from SEQ ID NOs: 43-74, 84-90, and 120-127. In some embodiments, the antigen-binding domain is a VHH domain, and the VHH domain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence set forth in SEQ ID NO: 44. In some embodiments, the antigen-binding domain comprises an amino acid sequence selected from SEQ ID NOs: 43-74, 84-90, and 120-127. In some embodiments, the antigen-binding domain comprises the amino acid sequence set forth in SEQ ID NO: 44.

[0048] In one aspect, provided herein is an FcRn / antigen-binding molecule comprising a first heavy chain, wherein the first heavy chain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 109, 110, 137-176, 180, and 250-295. In some embodiments, the first heavy chain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 180. In some embodiments, the first heavy chain comprises or consists of any one of the amino acid sequences of SEQ ID NOs: 109, 110, 137-176, 180, and 250-295. In some embodiments, the first heavy chain comprises or consists of the amino acid sequence of SEQ ID NO: 180. In some embodiments, the first heavy chain further comprises one of additional amino acids added at the C-terminus, and one of the additional amino acids is optionally selected from A, AG, GG, and PP.

[0049] In some embodiments, the FcRn / antigen-binding molecule further comprises a second heavy chain, wherein the second heavy chain consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the second heavy chain consists of the amino acid sequence of SEQ ID NO: 8.

[0050] In some embodiments, the FcRn / antigen-binding molecule further comprises a light chain, and the heavy chain comprises, or consists of, an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 109, and the light chain comprises, or consists of, an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 107. In some embodiments, the heavy chain comprises, or consists of, the amino acid sequence of SEQ ID NO: 109, and the light chain comprises, or consists of, the amino acid sequence of SEQ ID NO: 107.

[0051] Also provided are one or more isolated polynucleotides encoding any FcRn / antigen-binding molecule described herein or any antigen-binding domain described herein.

[0052] Also provided is an expression vector comprising any one or more isolated polynucleotides described herein.

[0053] Also provided is a host cell comprising any one or more isolated polynucleotides or any expression vector described herein.

[0054] Also provided is a method for producing an FcRn / antigen-binding molecule or an antigen-binding domain, the method comprising culturing a host cell described herein under conditions that allow for the expression of the FcRn / antigen-binding molecule or the antigen-binding domain.

[0055] Also provided is a pharmaceutical composition comprising an FcRn / antigen-binding molecule described herein or an antigen-binding domain described herein and at least one pharmaceutically acceptable carrier.

[0056] Also provided is an FcRn / antigen-binding molecule described herein, or an antigen-binding domain described herein, or a pharmaceutical composition thereof, for use as a medicament.

[0057] Also provided is a method for reducing serum IgG in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of an FcRn / antigen-binding molecule described herein, or an antigen-binding domain described herein, or a pharmaceutical composition thereof.

[0058] Also provided is a method for treating an antibody-mediated disorder in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of an FcRn / antigen-binding molecule described herein, or an antigen-binding domain described herein, or a pharmaceutical composition thereof.

[0059] In some embodiments, the antibody-mediated disorder is an IgG-mediated disorder. In some embodiments, the antibody-mediated disorder is an autoimmune disease. In some embodiments, the autoimmune disease is allograft rejection, alopecia areata, ankylosing spondylitis, antiphospholipid syndrome, autoimmune Addison's disease, Alzheimer's disease, antineutrophil cytoplasmic autoantibody (ANCA), autoimmune diseases of the adrenal gland, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune myocarditis, autoimmune neutropenia, autoimmune oophoritis and orchitis, immune thrombocytopenia (ITP or idiopathic thrombocytopenic purpura), idiopathic thrombocytopeniapurpura), immune-mediated thrombocytopenia, or idiopathic immune thrombocytopenia), autoimmune urticaria, Behçet's disease, bullous pemphigoid (BP), myocarditis, Castleman's disease, celiac sprue dermatitis, chronic fatigue immune dysfunction syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), Churg-Strauss syndrome, cicatricial pemphigoid, CREST syndrome, cold agglutinin disease, Crohn's disease, dilated cardiomyopathy, discoid lupus erythematosus, acquired epidermolysis bullosa, essential mixed cryoglobulinemia, factor VIII deficiency, fibromyalgia-fibromyositis, glomerulonephritis, Graves' disease, Guillain-Barré syndrome, Goodpasture's syndrome, graft-versus-host disease (GVHD), Hashimoto's thyroiditis, hemophilia A, idiopathic inflammatory myopathy (IIM), idiopathic membranous neuropathy, idiopathic pulmonary fibrosis, IgA neuropathy, IgM polyneuropathy, immune-mediated necrotizing myopathy (IMNM), juvenile arthritis, Kawasaki disease, lichen planus, lichen sclerosus, lupus erythematosus, lupus nephritis, Ménière's disease, mixed connective tissue disease, mucous membrane pemphigoid, multiple sclerosis, type 1 diabetes, multifocal motor neuropathy (MMN), myasthenia gravis (MG), generalized myasthenia gravis (gMG), myositis, paraneoplastic bullous pemphigoid, pemphigoid gestationis, pemphigus vulgaris (PV), pemphigus foliaceus (PF), pernicious anemia, polyarteritis nodosa, polychondritis, polyglandular syndrome, polymyalgia rheumatica, polymyositis, dermatomyositis (DM), necrotizing autoimmune myopathy (NAM), anti-synthetase syndrome (ASyS), primary agammaglobulinemia, primary biliary cirrhosis, psoriasis, psoriatic arthritis, relapsing polychondritis, Raynaud's phenomenon, Reiter's syndrome, rheumatoid arthritis, sarcoidosis, scleroderma, Sjögren's syndrome, solid organ transplant rejection, stiff-person syndrome, systemic lupus erythematosus, Takayasu arteritis, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), temporal arteritis / giant cell arteritis, thrombotic thrombocytopenic purpura, ulcerative colitis, uveitis, dermatitis herpetiformis vasculitis, antineutrophil cytoplasmic antibody-associated vasculitis, vitiligo, and Wegener's granulomatosis.

[0060] In some embodiments, the FcRn / antigen-binding molecule or antigen-binding domain is administered to a subject either concomitantly with or sequentially to an additional therapeutic agent.

[0061] Also provided are the FcRn / antigen-binding molecules described herein or the antigen-binding domains described herein for use in the treatment of antibody-mediated disorders.

[0062] Also provided is the use of the FcRn / antigen-binding molecules described herein or the antigen-binding domains described herein for the manufacture of a medicament for treating antibody-mediated disorders.

Brief Description of the Drawings

[0063]

Figure 1

[0064]

Figure 2

[0065]

Figure 3A

Figure 3B

[0066]

Figure 4

[0067]

Figure 5

[0068]

Figure 6A

Figure 6B

[0069]

Figure 7A

Figure 7B

[0070]

Figure 8A

Figure 8B

[0071]

Figure 9A

Figure 9B

[0072]

Figure 10A

Figure 10B

[0073]

Figure 11

[0074]

Figure 12

[0075]

Figure 13

[0076]

Figure 14

[0077]

Figure 15A

Figure 15B

[0078]

Figure 16A

Figure 16B

[0079]

Figure 17

[0080]

Figure 18A

[0081]

Figure 18B

[0082]

Figure 19

[0083]

Figure 20

[0084]

Figure 21A

Figure 21B

Figure 21C

[0085]

Figure 22

[0086]

Figure 23A

Figure 23B

Best Mode for Carrying Out the Invention

[0087] The present disclosure provides an engineered FcRn binding molecule (FcRn / antigen-binding molecule) linked to one antigen-binding domain. In one aspect, an FcRn / antigen-binding molecule is provided that includes an FcRn binding molecule linked to the antigen-binding domain at the C-terminus, or the N-terminus, or a position other than the C-terminus or N-terminus. Also provided herein are nucleic acids, vectors, host cells, methods of manufacture encoding such FcRn / antigen-binding molecules, and methods for their use in the treatment of antibody-mediated disorders.

[0088] Definitions As used herein, the term “FcRn” refers to the neonatal Fc receptor. Exemplary FcRn molecules include human FcRn encoded by the FCGRT gene as shown in RefSeq NM 004107. The amino acid sequence of the corresponding protein is shown in RefSeq NP_004098.

[0089] As used herein, the term "FcRn-binding molecule" refers to any agent that specifically binds to FcRn. As used herein, the term "FcRn antagonist" refers to any agent that specifically binds to FcRn and inhibits the binding of an immunoglobulin to FcRn (e.g., human FcRn). In one embodiment, the FcRn antagonist comprises an Fc region (e.g., a variant Fc region disclosed herein), specifically binds to FcRn via the Fc region, and inhibits the binding of an immunoglobulin to FcRn. In one embodiment, the FcRn antagonist is not a full-length IgG antibody. In one embodiment, the FcRn antagonist comprises an antigen-binding domain that binds to a human target antigen and a variant Fc region. In one embodiment, the term "FcRn antagonist" refers to an antibody or an antigen-binding fragment thereof that specifically binds to FcRn via its antigen-binding domain or its Fc region and inhibits the binding of the Fc region of an immunoglobulin (e.g., an IgG autoantibody) to FcRn. As used herein, the term "FcRn / antigen-binding molecule" refers to any agent that specifically binds to FcRn and specifically binds to another human antigen. In some embodiments, the antigen is IgE or HSA. In some embodiments, the antigen is IgE. In some embodiments, the antigen is HSA.

[0090] As used herein, the term "affinity" or "binding affinity" refers to the strength of the binding interaction between two molecules. As used herein, the term "equilibrium dissociation constant" or "K D " refers to the tendency of the binding complex of two molecules to dissociate into two free molecules. Thus, as the binding affinity increases, K D decreases.

[0091] As used herein, the term "specifically binds" refers to the ability of any molecule to preferentially bind to a given target. For example, a molecule that specifically binds to a given target can bind to other molecules and generally bind with a lower affinity, as determined by, for example, an immunoassay, BIAcore™, KinExA 3000 instrument (Sapidyne Instruments, Boise, Id.), or other assays known in the art. In certain embodiments, a molecule that specifically binds to a given target has a K D or K D less than when binding to another target.

[0092] As used herein, the term "operably linked" refers to the linkage of polynucleotide sequence elements that are in a functional relationship. For example, a polynucleotide sequence is operably linked when it is placed in a functional relationship with another polynucleotide sequence. In some embodiments, a transcriptional regulatory polynucleotide sequence, such as a promoter, enhancer, or other expression control element, is operably linked to a polynucleotide sequence encoding a protein if it affects the transcription of the polynucleotide sequence encoding the protein. The operably linked elements can be contiguous or non-contiguous.

[0093] As used herein, the term "linked" refers to a physical linkage (e.g., directly or indirectly linked) between amino acid sequences (e.g., different segments, regions, fragments, or domains). The linked regions, fragments, domains, and segments of the FcRn / antigen-binding molecules of the present disclosure can be contiguous or non-contiguous (e.g., linked to each other via a linker). In some embodiments, the linkage is a covalent bond. In some embodiments, the linkage is a non-covalent bond.

[0094] As used herein, the term "covalently linked" refers to the linking of two molecules or chemical moieties by a covalent bond. In some embodiments, the covalent bond is a peptide bond or a disulfide bond. As used herein, the term "fused" refers to the linking of two peptides by a peptide bond or a peptide linker. In some embodiments, two proteins are directly and continuously fused together by a peptide bond. In some embodiments, two proteins are indirectly and discontinuously fused via a peptide linker. In some embodiments, one protein is fused to the peptide linker at a first position by a peptide bond, and a second protein is fused to the peptide linker at a second position by a peptide bond. As used herein, the term "non-covalently linked" refers to the linking of two molecules or chemical moieties by non-covalent interactions or non-covalent bonds. In some embodiments, the non-covalent interactions or non-covalent bonds include hydrogen bonds, electrostatic bonds or interactions, halogen bonds, pi-stacking, and van der Waals interactions.

[0095] The determination of the "percent identity" between two sequences (e.g., amino acid sequences or nucleic acid sequences) can be accomplished using a mathematical algorithm. Specific non-limiting examples of mathematical algorithms used for comparing two sequences are the algorithms of Karlin S & Altschul SF, (1990) PNAS 87:2264-2268, as modified as in Karlin S & Altschul SF, (1993) PNAS 90:5873-5877, each of which is incorporated herein by reference in its entirety. Such algorithms are incorporated into the NBLAST and XBLAST programs of Altschul SF et al., (1990) J Mol Biol 215:403, which is incorporated herein by reference in its entirety. BLAST nucleotide searches can be performed with the NBLAST nucleotide program parameter set, e.g., score = 100, wordlength = 12, to obtain nucleotide sequences homologous to the nucleic acid molecules described herein. BLAST protein searches can be performed with the XBLAST program parameter set, e.g., score = 50, wordlength = 3, to obtain amino acid sequences homologous to the protein molecules described herein. To obtain gapped alignments for comparison purposes, gapped BLAST can be used as described in Altschul SF et al., (1997) Nuc Acids Res 25:3389-3402, which is incorporated herein by reference in its entirety. Alternatively, PSI BLAST can be used to perform iterative searches to detect distant relationships between molecules. Id. When utilizing the BLAST, gapped BLAST, and PSI BLAST programs, the default parameters of each program (e.g., of XBLAST and NBLAST) can be used (see, e.g., National Center for Biotechnology Information (NCBI) on the worldwide web, ncbi.nlm.nih.gov).Another specific non-limiting example of a mathematical algorithm used for array comparison is the algorithm of Myers and Miller, (1988) CABIOS 4:11-17, which is hereby incorporated by reference in its entirety. Such an algorithm is incorporated into the ALIGN program (version 2.0), which is part of the GCG sequence alignment software package. When utilizing the ALIGN program to compare amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4 can be used.

[0096] Percent identity between two arrays can be determined with or without allowing gaps using techniques similar to those described above. In calculating percent identity, typically only exact matches are counted.

[0097] As used herein, the terms “antibody” and “antibodies” include full-length antibodies, antigen-binding fragments of full-length antibodies, and molecules containing antibody CDRs, VH domains (VH), or VL domains (VL). Examples of antibodies include monoclonal antibodies, recombinantly produced antibodies, monospecific antibodies, multispecific antibodies (including bispecific antibodies), human antibodies, humanized antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies containing two heavy chains and two light chain molecules, antibody light chain monomers, antibody heavy chain monomers, antibody light chain dimers, antibody heavy chain dimers, antibody light chain-heavy chain pairs, intrabodies, heteroconjugate antibodies, antibody-drug conjugates, single domain antibodies (sdAb), monovalent antibodies, single chain antibodies or single chain Fv (scFv), camelid antibodies, humanized antibodies, affibody molecules, VHH fragments, Fab fragments, F(ab’)2 fragments, disulfide-linked Fv (sdFv), anti-idiotype (anti-Id) antibodies (including, e.g., anti-anti-Id antibodies), and antigen-binding fragments of any of the foregoing. Antibodies can be of any isotype (e.g., IgG, IgE, IgM, IgD, IgA, or IgY), any subclass (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, or IgA2), or species (e.g., mouse IgG2a or IgG 2b can be of an immunoglobulin molecule of ().

[0098] As used herein, the term "antigen-binding domain" (or "antigen binding domain") refers to any polypeptide that specifically binds to an antigen. Examples of antigen-binding domains include antibodies such as Fab fragments, F(ab’)2 fragments, disulfide-linked Fv (sdFv), single-chain Fv (scFv), CDRs, VH domains (VH), VL domains (VL), single-domain antibodies (sdAb), VHH fragments, camelid antibodies, and polypeptides derived from any of the above antigen-binding fragments. The term also encompasses synthetic antigen-binding proteins or antibody mimetic proteins such as anticalin and DARPin.

[0099] In some embodiments, the antigen-binding domain is a VHH fragment. In some embodiments, the VHH fragment has one or more additional amino acids at its C-terminus. In some embodiments, the one or more additional amino acids are selected from the group consisting of A, AG, GG, and PP.

[0100] As used herein, the term "Fc region" refers to the portion of an immunoglobulin formed by the Fc domains of its two heavy chains. The Fc region can be a wild-type Fc region (native Fc region) or a variant Fc region. The native Fc region is a homodimer. The Fc region can be derived from any native immunoglobulin. In some embodiments, the Fc region is formed from an IgA, IgD, IgE, or IgG heavy chain constant region. In some embodiments, the Fc region is formed from an IgG heavy chain constant region. In some embodiments, the IgG heavy chain is an IgG1, IgG2, IgG3, or IgG4 heavy chain constant region. In some embodiments, the Fc region is formed from an IgG1 heavy chain constant region. In some embodiments, the IgG1 heavy chain constant region includes the G1m1(a), G1m2(x), G1m3(f), or G1m17(z) allotype. See, e.g., Jefferis and Lefranc (2009) mAbs 1(4):332-338, and de Taeye et al., (2020) Front Immunol. 11:740, which are incorporated herein by reference in their entirety.

[0101] As used herein, the term "variant Fc region" refers to a variant of the Fc region that has one or more changes relative to the native Fc region. The modifications can include amino acid substitutions, additions and / or deletions, ligation of additional moieties, and / or modification of native glycans. This term encompasses heterodimeric Fc regions in which each of the constituent Fc domains is different. This term also encompasses single-chain Fc regions in which the constituent Fc domains are linked together by a linker moiety.

[0102] As used herein, the term "Fc domain" refers to the portion of a single immunoglobulin heavy chain that includes both the CH2 and CH3 domains of the antibody. In some embodiments, the Fc domain includes at least a portion of the hinge (e.g., upper, middle, and / or lower hinge region) region, the CH2 domain, and the CH3 domain. In some embodiments, the Fc domain does not include the hinge region.

[0103] As used herein, the term "hinge region" refers to the portion of the heavy chain molecule that links the CH1 domain to the CH2 domain. In some embodiments, the hinge region is up to 70 amino acid residues in length. In some embodiments, this hinge region contains approximately 11 to 17 amino acid residues, is flexible, and thus allows the two N-terminal antigen-binding regions to move independently. In some embodiments, the hinge region is 12 amino acid residues in length. In some embodiments, the hinge region is 15 amino acid residues in length. In some embodiments, the hinge region is 62 amino acid residues in length. The hinge region can be subdivided into three different domains: an upper, a middle, and a lower hinge domain. The FcRn / antigen-binding molecule of the present disclosure can include all or any part of the hinge region. In some embodiments, the hinge region is derived from an IgG1 antibody. In some embodiments, the hinge region comprises the amino acid sequence EPKSCDKTHTCPPCP (SEQ ID NO: 179).

[0104] As used herein, the term "FcRn-binding fragment" refers to a portion of an FcRn-binding molecule, e.g., a portion of the Fc region, that is sufficient to confer FcRn binding.

[0105] As used herein, the terms "one-armed", "one armed", "one-arm", "one arm", or "OA" refer to an FcRn / antigen-binding molecule that comprises an FcRn-binding molecule linked to only one antigen-binding domain. In some embodiments, "one-armed", "one armed", "one-arm", "one arm", or "OA" is an FcRn / antigen-binding molecule that comprises an Fc region that includes the Fc domains of two heavy chains, wherein one of the Fc domains of the two heavy chains is linked to the antigen-binding domain and the other Fc domain of the two heavy chains is not linked to the antigen-binding domain. In some embodiments, the antigen-binding domain is linked to the C-terminus of one of the Fc domains of the two heavy chains. In some embodiments, the antigen-binding domain is linked to the N-terminus of one of the Fc domains of the two heavy chains. In some embodiments, the antigen-binding domain is linked to a position other than the N-terminus or C-terminus of one of the Fc domains of the two heavy chains. The linkage can be a covalent or non-covalent bond. In some embodiments, the antigen-binding domain is fused to the C-terminus of one of the Fc domains of the two heavy chains. In some embodiments, the antigen-binding domain is fused to the N-terminus of one of the Fc domains of the two heavy chains. In some embodiments, the antigen-binding domain is fused to a position other than the N-terminus or C-terminus of one of the Fc domains of the two heavy chains.

[0106] As used herein, the terms "two-armed", "two armed", "two-arm", "two arm", or "TA" refer to an FcRn / antigen-binding molecule that includes an FcRn-binding molecule linked to two antigen-binding domains. In some embodiments, "two-armed", "two armed", "two-arm", "two arm", or "TA" refers to an FcRn / antigen-binding molecule that includes an Fc region that includes the Fc domains of two heavy chains, wherein each of the Fc domains of the two heavy chains is linked to an antigen-binding domain. In some embodiments, the antigen-binding domain is linked to the C-terminus of each of the Fc domains of the two heavy chains. In some embodiments, the antigen-binding domain is linked to the N-terminus of each of the Fc domains of the two heavy chains. In some embodiments, the antigen-binding domain is linked to a position other than the N-terminus or C-terminus of each of the Fc domains of the two heavy chains. In some embodiments, one of the antigen-binding domains is linked to the N-terminus of one of the Fc domains of the two heavy chains, and the other antigen-binding domain is linked to the C-terminus of the other Fc domain of the two heavy chains. In some embodiments, one of the antigen-binding domains is linked to a position other than the N-terminus or C-terminus of one of the Fc domains of the two heavy chains, and the other antigen-binding domain is linked to the N-terminus of the other Fc domain of the two heavy chains. In some embodiments, one of the antigen-binding domains is linked to a position other than the N-terminus or C-terminus of one of the Fc domains of the two heavy chains, and the other antigen-binding domain is linked to the C-terminus of the other Fc domain of the two heavy chains. The linkage can be a covalent or non-covalent bond. In some embodiments, the antigen-binding domain is fused to the C-terminus of each of the Fc domains of the two heavy chains. In some embodiments, the antigen-binding domain is fused to the N-terminus of each of the Fc domains of the two heavy chains. In some embodiments, the antigen-binding domain is fused to a position other than the N-terminus or C-terminus of each of the Fc domains of the two heavy chains.In some embodiments, one of the antigen-binding domains is fused to the N-terminus of one of the two heavy-chain Fc domains, and the other antigen-binding domain is fused to the C-terminus of the other Fc domain of the two heavy chains. In some embodiments, one of the antigen-binding domains is fused at a position other than the N-terminus or C-terminus of one of the two heavy-chain Fc domains, and the other antigen-binding domain is fused to the N-terminus of the other Fc domain of the two heavy chains. In some embodiments, one of the antigen-binding domains is fused at a position other than the N-terminus or C-terminus of one of the two heavy-chain Fc domains, and the other antigen-binding domain is fused to the C-terminus of the other Fc domain of the two heavy chains.

[0107] As used herein, the term "EU position" refers to the amino acid position in the EU numbering convention for the Fc region as described in Edelman, G. M. et al. Proc. Natl. Acad. USA, 63, 78 - 85 (1969), and Rabat et al., "Sequences of Proteins of Immunological Interest," U.S. Dept. Health and Human Services, 5 th edition, 1991.

[0108] As used herein, the term "antibody-mediated disorder" refers to any disorder in which the symptoms of the disorder are caused by abnormal levels of one or more (auto)antibodies in a subject. As used herein, the term "autoantibody-mediated disorder" refers to any disease or disorder in which the underlying pathology is at least partially caused by pathogenic IgG autoantibodies.

[0109] As used herein, the terms "treating", "treatment", and "treat" refer to the therapeutic or prophylactic measures described herein. A "treatment" method is used to prevent, cure, delay, reduce the severity of, or improve one or more symptoms of a disease or disorder, or a recurrent disease or disorder, or to extend the lifespan of a subject beyond that expected in the absence of such treatment, by administering a polypeptide to a subject having or susceptible to such a disease or disorder. In some embodiments, a "treatment" method involves administering a polypeptide to a subject having or predisposed to have a disease or disorder, to prevent, cure, delay, reduce the severity of, or remit the disease or disorder, or a recurrent disease or disorder.

[0110] As used herein, in the context of performing a therapy on a subject, the term "effective amount" refers to the amount of the therapy that achieves the desired prophylactic or therapeutic effect.

[0111] As used herein, the term "dose" or "dosage" refers to the amount of an agent administered to a subject in a single administration.

[0112] As used herein, both the terms "fixed dose" and "uniform dose" refer to a dose that does not vary based on the characteristics of the subject (e.g., weight, e.g., within a set range; gender; age, e.g., within a set range, etc.).

[0113] As used herein, the term "equivalent dosage" refers to the dosages of the first and second therapeutic agents where the number of molecules of the first and second therapeutic agents is substantially the same. In some embodiments, the equivalent dosage is an equimolar dosage. As used herein, the term "equimolar dosage" refers to the dosages of the first and second therapeutic agents where the number of moles of the first and second agents is the same. In some embodiments, the first agent is an FcRn / antigen-binding molecule and the second agent is efgartigimod. In some embodiments, the equivalent dosage is calculated using the observed molecular weights of the first and second agents. In some embodiments, the equivalent dosage is calculated using the predicted molecular weights of the first and second agents. In some embodiments, the equivalent dosage is calculated using the observed molecular weight of the first agent and the predicted molecular weight of the second agent. In some embodiments, the equivalent dosage is calculated using the predicted molecular weight of the first agent and the observed molecular weight of the second agent.

[0114] As used herein, the terms "pharmacodynamics" and "PD" refer to the biological effects of a therapeutic agent on an organism. In some embodiments, the biological effect is the modulation of the amount of circulating IgG in an organism administered the therapeutic agent. In some embodiments, the biological effect is the modulation of the amount of circulating albumin in an organism administered the therapeutic agent. As used herein, the term "improved pharmacodynamics" or "improved PD" refers to an improvement in the desired biological effect in an organism administered the therapeutic agent. In some embodiments, improved pharmacodynamics includes a reduction in the amount of circulating IgG in a subject. In some embodiments, improved pharmacodynamics includes the maintenance of the amount of circulating albumin in a subject. In some embodiments, improved pharmacodynamics includes a reduction in the amount of circulating IgG in a subject and the maintenance of the amount of circulating albumin in a subject. In some embodiments, the therapeutic agent is an FcRn / antigen-binding molecule.

[0115] As used herein, the terms "pharmacokinetics" and "PK" refer to the effect of an organism on a therapeutic agent administered to the organism. In some embodiments, the effect is the metabolism and / or clearance of the therapeutic agent. In some embodiments, PK refers to the rate of metabolism and / or clearance of a therapeutic agent. As used herein, the term "improved pharmacokinetics" or "improved PK" refers to an improvement in the desired effect of an organism on a therapeutic agent administered to the organism. In some embodiments, improved pharmacokinetics includes an increase in the half-life (T 1 / 2 )), clearance, or area under the curve (AUC) of a therapeutic agent in a subject. In some embodiments, the therapeutic agent is an FcRn / antigen-binding molecule.

[0116] As used herein, the term "subject", or "patient", or "participant" includes any human or non-human animal. In one embodiment, the subject, or patient, or participant is a human or non-human mammal. In one embodiment, the subject, or patient, or participant is a human.

[0117] As used herein, the term "about" or "approximately" when referring to a measurable value such as a dosage amount encompasses a variation of ±20%, ±15%, ±10%, ±5%, ±1%, or ±0.1% of the given value or range as appropriate to carry out the methods disclosed herein.

[0118] As used herein, the term "molecular weight" can refer to "predicted molecular weight" or "observed molecular weight". The "predicted molecular weight" of a protein is the sum of the molecular weights of all the amino acids in the protein. In certain circumstances, the "predicted molecular weight" can differ from the "observed molecular weight" of the molecule. In some embodiments, these differences can occur in a protein due to changes in glycosylation, glycanation, ubiquitination, phosphorylation, or protein cleavage of the protein or an additional protein complex with a given protein.

[0119] FcRn / antigen-binding molecule The present disclosure provides FcRn / antigen-binding molecules or fragments thereof. In some embodiments, the FcRn / antigen-binding molecules disclosed herein comprise an FcRn-binding molecule and only one antigen-binding domain. The FcRn-binding molecule can be any of the FcRn-binding molecules described herein. Similarly, the antigen-binding domain can be any of the antigen-binding domains described herein.

[0120] In some embodiments, the antigen-binding domain is linked to the C-terminus of the FcRn-binding molecule. In some embodiments, the antigen-binding domain is linked to the N-terminus of the FcRn-binding molecule. In some embodiments, the antigen-binding domain is linked to the FcRn-binding molecule at a position other than the C-terminus or N-terminus. The antigen-binding domain may be covalently or non-covalently linked to the FcRn-binding molecule.

[0121] In some embodiments, the antigen-binding domain is fused to the C-terminus of the FcRn-binding molecule. In some embodiments, the antigen-binding domain is fused to the N-terminus of the FcRn-binding molecule. In some embodiments, the antigen-binding domain is fused to the FcRn-binding molecule at a position other than the C-terminus or N-terminus.

[0122] In some embodiments, the FcRn-binding molecule is an Fc region, such as a variant Fc region. In some embodiments, the antigen-binding domain is linked or fused to the C-terminus of one of the Fc domains of the variant Fc region. In some embodiments, the antigen-binding domain is linked or fused to the N-terminus of one of the Fc domains of the variant Fc region. In some embodiments, the antigen-binding domain is linked or fused to the FcRn-binding molecule at a position other than the C-terminus or N-terminus.

[0123] In some embodiments, the antigen-binding domain may be directly linked to or directly fused with the N-terminus or C-terminus of the FcRn-binding molecule. In some embodiments, the antigen-binding domain is linked to the N-terminus or C-terminus of the FcRn-binding molecule via a linker. In some embodiments, the linker is a non-cleavable linker.

[0124] In some embodiments, the antigen-binding domain may be directly linked (e.g., fused) to the N-terminus or C-terminus of the Fc domain. In some embodiments, the antigen-binding domain is linked to the N-terminus or C-terminus of the Fc domain via a linker. The linker can be any suitable linker including those described herein.

[0125] FcRn-binding molecule The FcRn-binding molecules disclosed herein include any molecule that binds to FcRn, and the molecule includes, but is not limited to, any anti-FcRn antibody, any anti-FcRn binding region, or any Fc domain or Fc region.

[0126] In some embodiments, the FcRn-binding molecule is an FcRn antagonist that includes any molecule that binds to and inhibits FcRn, and the molecule includes, but is not limited to, any anti-FcRn antibody, any anti-FcRn binding region, or any Fc domain or Fc region.

[0127] In some embodiments, the FcRn-binding molecules disclosed herein include two, three, or four FcRn-binding regions, such as Fc regions.

[0128] In some embodiments, the FcRn-binding molecules disclosed herein include one or more Fc regions or their FcRn-binding fragments in combination with one or more antigen-binding domains (e.g., sdAb, Fab fragment, scFv, or antibody mimetic).

[0129] Any Fc region can be altered to produce a variant Fc region disclosed herein. Generally, the Fc region or its FcRn-binding fragment is from a human immunoglobulin. However, it is understood that the Fc region can be derived from an immunoglobulin of any other mammalian species, including, for example, camelid species, rodents (e.g., mouse, rat, rabbit, guinea pig), or non-human primate (e.g., chimpanzee, macaque) species. Also, the Fc region or its FcRn-binding portion can be derived from any immunoglobulin class, including IgM, IgG, IgD, IgA, and IgE, and any immunoglobulin isotype, including IgG1, IgG2, IgG3, and IgG4. In one embodiment, the Fc region is an IgG Fc region (e.g., a human IgG region). In one embodiment, the Fc region is an IgG1 Fc region (e.g., a human IgG1 region). In one embodiment, the Fc region is a chimeric Fc region that includes portions of several different Fc regions. Suitable examples of chimeric Fc regions are described in US2011 / 0243966A1, which is incorporated herein by reference in its entirety. Various Fc region gene sequences (e.g., human constant region gene sequences) are available in the form of publicly available deposits.

[0130] The Fc region may be further cleaved to produce its minimal FcRn-binding fragment or may be internally deleted. The ability of an Fc region fragment to bind to FcRn can be determined using any binding assay recognized in the art, such as ELISA.

[0131] To enhance the manufacturability of the FcRn-binding molecules disclosed herein and FcRn / antigen-binding molecules containing them, the Fc region as a component preferably does not contain any non-disulfide-bonded cysteine residues. Thus, in one embodiment, the Fc region does not contain free cysteine residues.

[0132] In some embodiments, any Fc variant or its FcRn-binding fragment that specifically binds to FcRn with increased affinity and reduced pH-dependence relative to the native Fc region can be used herein. In one embodiment, the variant Fc region comprises amino acid changes, substitutions, insertions, and / or deletions that confer the desired characteristics. In some embodiments, the FcRn-binding molecule comprises a variant Fc region or its FcRn-binding fragment, and the variant Fc region or its FcRn-binding fragment binds to FcRn with higher affinity at pH 5.5 compared to the corresponding wild-type Fc region. In some embodiments, the FcRn-binding molecule comprises a variant Fc region or its FcRn-binding fragment, and the variant Fc region or its FcRn-binding fragment binds to FcRn with higher affinity at pH 6.0 and / or pH 7.4 compared to the corresponding wild-type Fc region. In some embodiments, the FcRn-binding molecule comprises a variant Fc region or its FcRn-binding fragment, and the variant Fc region or its FcRn-binding fragment binds to FcRn with higher affinity at both acidic and neutral pHs compared to the corresponding wild-type Fc region.

[0133] In some embodiments, the variant Fc region is derived from the Fc region of any native immunoglobulin. In some embodiments, the native immunoglobulin is a human immunoglobulin. In some embodiments, the immunoglobulin is IgA, IgD, IgE, or IgG. In some embodiments, the immunoglobulin is IgG. In some embodiments, the immunoglobulin is human IgA, human IgD, human IgE, or human IgG. In some embodiments, the immunoglobulin is human IgG. In some embodiments, IgG is IgG1, IgG2, IgG3, or IgG4. In some embodiments, the human IgG is human IgG1, human IgG2, human IgG3, or human IgG4. In some embodiments, the variant Fc region varies from the human IgG1 Fc region. In some embodiments, the human IgG1 Fc region comprises the G1m1(a), G1m2(x), G1m3(f), or G1m17(z) allotype.

[0134] In some embodiments, the FcRn binding molecule is an FcRn antagonist.

[0135] In some embodiments, the variant Fc region or its FcRn binding fragment comprises or consists of at least one Fc domain. In some embodiments, the variant Fc region comprises or consists of two Fc domains. In some embodiments, the Fc domains are the same. In some embodiments, the Fc domains are different. In certain embodiments, at least one of the variant Fc domains or FcRn binding fragments described herein comprises at least one amino acid or at least two amino acids selected from the following: 237M, 238A, 239K, 248I, 250A, 250F, 250I, 250M, 250Q, 250S, 250V, 250W, 250Y, 252F, 252W, 252Y, 254T, 255E, 256D, 256E, 256Q, 257A, 257G, 257I, 257L, 257M, 257N, 257S, 257T, 257V, 258H, 265A, 270F, 286A, 286E, 289H, 297A, 298G, 303A, 305A, 307A, 307D, 307F, 307G, 307H, 307I, 307K, 307L, 307M, 307N, 307P, 307Q, 307R, 307S, 307V, 307W, 307Y, 308A, 308F, 308I, 308L, 308M, 308P, 308Q, 308T, 309A, 309D, 309E, 309P, 309R, 311A, 311H, 311I, 312A, 312H, 314K, 314R, 315A, 315H, 317A, 325G, 332V, 334L, 360H, 376A, 378V, 380A, 382A, 384A, 385D, 385H, 386P, 387E, 389A, 389S, 424A, 428A, 428D, 428F, 428G, 428H, 428I, 428K, 428L, 428N, 428P, 428Q, 428S, 428T, 428V, 428W, 428Y, 433K, 434A, 434F, 434H, 434S, 434W, 434Y, 436H, 436I, and 436F, and the positions are defined according to EU numbering.EU numbering refers to the convention for the Fc region as described in Edelman, G.M. et al., Proc. Natl. Acad. Sci. USA, 63:78 - 85 (1969), and Kabat et al., “Sequences of Proteins of Immunological Interest”, U.S. Dept. Health and Human Services, 5th th edition, 1991. In some embodiments, at least one of the variant Fc domains or FcRn - binding fragments described herein contains 2, 3, 4, or 5 amino acids selected from the following: 237M, 238A, 239K, 248I, 250A, 250F, 250I, 250M, 250Q, 250S, 250V, 250W, 250Y, 252F, 252W, 252Y, 254T, 255E, 256D, 256E, 256Q, 257A, 257G, 257I, 257L, 257M, 257N, 257S, 257T, 257V, 258H, 265A, 270F, 286A, 286E, 289H, 297A, 298G, 303A, 305A, 307A, 307D, 307F, 307G, 307H, 307I, 307K, 307L, 307M, 307N, 307P, 307Q, 307R, 307S, 307V, 307W, 307Y, 308A, 308F, 308I, 308L, 308M, 308P, 308Q, 308T, 309A, 309D, 309E, 309P, 309R, 311A, 311H, 311I, 312A, 312H, 314K, 314R, 315A, 315H, 317A, 325G, 332V, 334L, 360H, 376A, 378V, 380A, 382A, 384A, 385D, 385H, 386P, 387E, 389A, 389S, 424A, 428A, 428D, 428F, 428G, 428H, 428I, 428K, 428L, 428N, 428P, 428Q, 428S, 428T, 428V, 428W, 428Y, 433K, 434A, 434F, 434H, 434S, 434W, 434Y, 436H, 436I, and 436F, where the positions are defined according to EU numbering and any combination is contemplated.

[0136] In certain embodiments, at least one of the variant Fc domains or FcRn binding fragments described herein, when numbered by the EU index as described in Kabat, contains at least one non-naturally occurring amino acid or at least two non-naturally occurring amino acids selected from the following: 234, 235, 236, 239, 240, 241, 243, 244, 245, 247, 252, 254, 256, 262, 263, 264, 265, 266, 267, 269, 296, 297, 298, 299, 313, 325, 326, 327, 328, 329, 330, 332, 333, and 334. Optionally, at least one of the variant Fc domains may contain non-naturally occurring amino acid residues at additional and / or alternative positions known to those of skill in the art (see, e.g., U.S. Pat. Nos. 5,624,821, 6,277,375, 6,737,056, PCT Patent Publications 01 / 58957, 02 / 06919, 04 / 016750, 04 / 029207, 04 / 035752, and 05 / 040217, the contents of which are hereby incorporated by reference in their entirety).

[0137] In certain embodiments, at least one of the variant Fc domains comprises at least one non-natural amino acid or at least two non-natural amino acids selected from the group consisting of 234D, 234E, 234N, 234Q, 234T, 234H, 234Y, 234I, 234V, 234F, 235A, 235D, 235R, 235W, 235P, 235S, 235N, 235Q, 235T, 235H, 235Y, 235I, 235V, 235F, 236E, 239D, 239E, 239N, 239Q, 239F, 239T, 239H, 239Y, 240I, 240A, 240T, 240M, 241W, 241L, 241Y, 241E, 241R, 243W, 243L, 243Y, 243R, 243Q, 244H, 245A, 247V, 247G, 252Y, 254T, 256E, 262I, 262A, 262T, 262E, 263I, 263A, 263T, 263M, 264L, 264I, 264W, 264T, 264R, 264F, 264M, 264Y, 264E, 265G, 265N, 265Q, 265Y, 265F, 265V, 265I, 265L, 265H, 265T, 266I, 266A, 266T, 266M, 267Q, 267L, 269H, 269Y, 269F, 269R, 296E, 296Q, 296D, 296N, 296S, 296T, 296L, 296I, 296H, 269G, 297S, 297D, 297E, 298H, 298I, 298T, 298F, 299I, 299L, 299A, 299S, 299V, 299H, 299F, 299E, 313F, 325Q, 325L, 325I, 325D, 325E, 325A, 325T, 325V, 325H, 327G, 327W, 327N, 327L, 328S, 328M, 328D, 328E, 328N, 328Q, 328F, 328I, 328V, 328T, 328H, 328A, 329F, 329H, 329Q, 330K, 330G, 330T, 330C, 330L, 330Y, 330V, 330I, 330F, 330R, 330H, 332D, 332S, 332W, 332F, 332E, 332N, 332Q, 332T, 332H, 332Y, and 332A when numbered by the EU index as described in Kabat.Optionally, at least one of the variant Fc domains may contain additional and / or alternative non-naturally occurring amino acid residues known to those of skill in the art (see, e.g., U.S. Pat. Nos. 5,624,821, 6,277,375, 6,737,056, PCT Patent Publications Nos. 01 / 58957, 02 / 06919, 04 / 016750, 04 / 029207, 04 / 035752, and 05 / 040217, the contents of which are hereby incorporated by reference in their entirety).

[0138] Other known Fc domain variants that can be used in the compositions disclosed herein are described in Ghetie et al, 1997, Nat. Biotech. 15:637-40, Duncan et al, 1988, Nature 332:563-564, Lund et al, 1991, J. Immunol, 147:2657-2662, Lund et al, 1992, Mol. Immunol, 29:53-59, Alegre et al, 1994, Transplantation 57:1537-1543, Hutchins et al, 1995, Proc Natl. Acad Sci USA, 92:11980-11984, Jefferis et al, 1995, Immunol Lett., 44:111-117, Lund et al, 1995, Faseb J., 9:115-119, Jefferis et al, 1996, Immunol Lett., 54:101-104, Lund et al, 1996, J. Immunol, 157:4963-4969, Armour et al, 1999, Eur J Immunol 29:2613-2624, Idusogie et al, 2000, J. Immunol, 164:4178-4184, Reddy et al, 2000, J. Immunol, 164:1925-1933, Xu et al, 2000, Cell Immunol, 200:16-26, Idusogie et al, 2001, J. Immunol, 166:2571-2575, Shields et al, 2001, J Biol. Chem., 276:6591-6604, Jefferis et al, 2002, Immunol Lett., 82:57-65, Presta et al, 2002, Biochem Soc Trans., 30:487 - 490), U.S. Patent Nos. 5,624,821, 5,885,573, 5,677,425, 6,165,745, 6,277,375, 5,869,046, 6,121,022, 5,624,821, 5,648,260, 6,528,624, 6,194,551, 6,737,056, 6,821,505, 6,277,375, U.S. Patent Publication No. 2004 / 0002587, and PCT Publication Nos. 94 / 29351, 99 / 58572, 00 / 42072, 02 / 060919, 04 / 029207, 04 / 099249, 04 / 063351, including but not limited to those disclosed therein, and the contents of these documents are hereby incorporated by reference in their entirety.

[0139] In one embodiment, the variant Fc region or its FcRn-binding fragment comprises or consists of two Fc domains. In one embodiment, the variant Fc region or its FcRn-binding fragment comprises at least one Fc domain, and at least one Fc domain comprises the amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively. In one embodiment, the variant Fc region or its FcRn-binding fragment comprises at least one Fc domain, and at least one Fc domain comprises the amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively. In one embodiment, the variant Fc region or its FcRn-binding fragment comprises one Fc domain comprising the amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively, and a second Fc domain comprising the amino acids K and F at EU positions 433 and 434, respectively. In one embodiment, the variant Fc region or its FcRn-binding fragment comprises one Fc domain comprising the amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively, and a second Fc domain comprising the amino acids K and F at EU positions 433 and 434, respectively. In one embodiment, the variant Fc region or its FcRn-binding fragment consists of two Fc domains, both of which comprise the amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively. In one embodiment, the variant Fc region or its FcRn-binding fragment consists of two Fc domains, both of which comprise the amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0140] In certain embodiments, at least one of the variant Fc domains or FcRn-binding fragments described herein is, hereinafter,

[0141] (i) Q and L at EU positions 250 and 428, respectively,

[0142] (ii) P and A at EU positions 308 and 434, respectively,

[0143] (iii) P and Y at EU positions 308 and 434, respectively, or

[0144] (iv) Combinations of amino acids selected from Y, E, and Y at EU positions 252, 286, and 434, respectively.

[0145] In certain embodiments, at least one of the variant Fc domains or FcRn binding fragments described herein comprises at least one amino acid substitution selected from G237M, P238A, S239K, K248I, T250A, T250F, T250I, T250M, T250Q, T250S, T250V, T250W, T250Y, M252F, M252W, M252Y, S254T, R255E, T256D, T256E, T256Q, P257A, P257G, P257I, P257L, P257M, P257N, P257S, P257T, P257V, E258H, D265A, D270F, N286A, N286E, T289H, N297A, S298G, V303A, V305A, T307A, T307D, T307F, T307G, T307H, T307I, T307K, T307L, T307M, T307N, T307P, T307Q, T307R, T307S, T307V, T307W, T307Y, V308A, V308F, V308I, V308L, V308M, V308P, V308Q, V308T, V309A, V309D, V309E, V309P, V309R, Q311A, Q311H, Q311I, D312A, D312H, L314K, L314R, N315A, N315H, K317A, N325G, I332V, K334L, K360H, D376A, A378V, E380A, E382A, N384A, G385D, G385H, Q386P, P387E, N389A, N389S, S424A, M428A, M428D, M428F, M428G, M428H, M428I, M428K, M428L, M428N, M428P, M428Q, M428S, M428T, M428V, M428W, M428Y, H433K, N434A, N434F, N434H, N434S, N434W, N434Y, Y436H, Y436I, and Y436F, and the positions are defined according to EU numbering.In some embodiments, at least one of the variant Fc domains or FcRn binding fragments described herein comprises 2, 3, 4, or 5 amino acid substitutions selected from the following: G237M, P238A, S239K, K248I, T250A, T250F, T250I, T250M, T250Q, T250S, T250V, T250W, T250Y, M252F, M252W, M252Y, S254T, R255E, T256D, T256E, T256Q, P257A, P257G, P257I, P257L, P257M, P257N, P257S, P257T, P257V, E258H, D265A, D270F, N286A, N286E, T289H, N297A, S298G, V303A, V305A, T307A, T307D, T307F, T307G, T307H, T307I, T307K, T307L, T307M, T307N, T307P, T307Q, T307R, T307S, T307V, T307W, T307Y, V308A, V308F, V308I, V308L, V308M, V308P, V308Q, V308T, V309A, V309D, V309E, V309P, V309R, Q311A, Q311H, Q311I, D312A, D312H, L314K, L314R, N315A, N315H, K317A, N325G, I332V, K334L, K360H, D376A, A378V, E380A, E382A, N384A, G385D, G385H, Q386P, P387E, N389A, N389S, S424A, M428A, M428D, M428F, M428G, M428H, M428I, M428K, M428L, M428N, M428P, M428Q, M428S, M428T, M428V, M428W, M428Y, H433K, N434A, N434F, N434H, N434S, N434W, N434Y, Y436H, Y436I, and Y436F, where the positions are defined according to EU numbering, and any combination of substitutions is contemplated.

[0146] In certain embodiments, at least one of the variant Fc domains or FcRn binding fragments described herein comprises the following:

[0147] (i) M252Y, S254T, T256E, H433K, and N434F,

[0148] (ii) T250Q and M428L,

[0149] (iii) V308P and N434A,

[0150] (iv) V308P and N434Y, or

[0151] (v) Comprising a combination of amino acid substitutions selected from M252Y, N286E, and N434Y.

[0152] In one embodiment, one, two, or more mutations (e.g., amino acid substitutions) have been introduced into the hinge region of the polypeptides described herein, whereby the number of cysteine residues in the hinge region has been altered (e.g., increased or decreased) as described, for example, in U.S. Patent No. 5,677,425, which is hereby incorporated by reference in its entirety. The number of cysteine residues in the hinge region may be altered, for example, to facilitate the assembly of the light and heavy chains, or to alter (e.g., increase or decrease) the stability of the polypeptide.

[0153] In one embodiment, one, two, or more amino acid mutations (e.g., substitutions, insertions, or deletions) are introduced into the Fc region, Fc domain, or its FcRn-binding fragment, altering (e.g., decreasing or increasing) the in vivo half-life of the polypeptide. For examples of mutations that alter (e.g., decrease or increase) the in vivo half-life of an antibody, see, e.g., WO 02 / 060919, WO 98 / 23289, WO 97 / 34631, and U.S. Pat. Nos. 5,869,046, 6,121,022, 6,277,375, and 6,165,745, the entireties of which are incorporated herein by reference. In certain embodiments, one, two, or more amino acid mutations (e.g., substitutions, insertions, or deletions) are introduced into the Fc region, Fc domain, or its FcRn-binding fragment, decreasing the in vivo half-life of the polypeptide. In other embodiments, one, two, or more amino acid mutations (e.g., substitutions, insertions, or deletions) are introduced into the Fc region, Fc domain, or its FcRn-binding fragment, increasing the in vivo half-life of the antibody. In one embodiment, the Fc region or Fc domain may have one or more amino acid mutations (e.g., substitutions) in the second constant (CH2) domain (residues 231-340 of human IgG1) and / or the third constant (CH3) domain (residues 341-447 of human IgG1), which are numbered according to the EU numbering system. In one embodiment, the constant region of IgG1 of the polypeptide described herein includes a substitution from methionine (M) to tyrosine (Y) at position 252, a substitution from serine (S) to threonine (T) at position 254, and a substitution from threonine (T) to glutamic acid (E) at position 256, which are numbered according to the EU numbering system. See U.S. Pat. No. 7,658,921, the entirety of which is incorporated herein by reference.This type of variant Fc domain, referred to as a "YTE variant", has been shown to exhibit a 4-fold increased half-life compared to the same antibody in its wild-type version (see Dall’Acqua WF et al., (2006) J Biol Chem 281:23514-24, which is hereby incorporated by reference in its entirety). In one embodiment, the polypeptide comprises an IgG constant region, and the IgG constant region comprises one, two, three, or more amino acid substitutions at positions 251-257, 285-290, 308-314, 385-389, and 428-436, which are numbered according to the EU numbering system.

[0154] In one embodiment, one, two, or more mutations (e.g., amino acid substitutions) are introduced into the Fc region, Fc domain, or FcRn-binding fragment thereof (e.g., CH2 domain (residues 231-340 of human IgG1) and / or CH3 domain (residues 341-447 of human IgG1, numbered according to the EU numbering system), and / or hinge region (residues 216-230 numbered according to the EU numbering system)) of the polypeptides described herein to increase or decrease the affinity of the antibody for Fc receptors (e.g., activating Fc receptors) on the surface of effector cells. Mutations in the Fc region, Fc domain, or FcRn-binding fragment thereof that decrease or increase the affinity of the antibody for Fc receptors, and techniques for introducing such mutations into Fc receptors or fragments thereof, are known to those of skill in the art. Examples of mutations in the Fc region, Fc domain, or FcRn-binding fragment thereof that can be made to alter the affinity of the variant Fc region or its FcRn-binding fragment for Fc receptors are described, for example, in Smith P et al., (2012) PNAS 109:6181-6186, U.S. Patent No. 6,737,056, and International Publications Nos. 02 / 060919, 98 / 23289, and 97 / 34631, all of which are hereby incorporated by reference in their entirety.

[0155] In one embodiment, one, two, or more amino acid substitutions are introduced within the Fc region, Fc domain, or its FcRn binding fragment, altering the effector function(s) of the polypeptide. For example, one or more amino acids selected from amino acid residues 234, 235, 236, 237, 239, 243, 267, 292, 297, 300, 318, 320, 322, 328, 330, 332, and 396, which are numbered according to the EU numbering system, can be replaced with different amino acid residues, whereby the polypeptide has an altered affinity for effector ligands but retains the antigen-binding ability of the parental polypeptide. The effector ligand with the altered affinity can be, for example, an Fc receptor. This approach is described in more detail in U.S. Patent Nos. 5,624,821 and 5,648,260, each of which is incorporated herein by reference in its entirety. In one embodiment, one or more amino acid substitutions are introduced within the Fc region or Fc domain of the polypeptides described herein to remove potential glycosylation sites on the Fc region or Fc domain, which can reduce Fc receptor binding (see, e.g., Shields RL et al., (2001) J Biol Chem 276:6591-604, which is incorporated herein by reference in its entirety). In one embodiment, one or more of the following mutations in the constant region of the polypeptides described herein, N297A substitution, N297Q substitution, L234A substitution, L234F substitution, L235A substitution, L235F substitution, L235V substitution, L237A substitution, S239D substitution, E233P substitution, L234V substitution, L235A substitution, C236 deletion, P238A substitution, S239D substitution, F243L substitution, D265A substitution, S267E substitution, L328F substitution, R292P substitution, Y300L substitution, A327Q substitution, P329A substitution, A330L substitution, I332E substitution, or P396L substitution can be made, which are numbered according to the EU numbering system.

[0156] In one embodiment, mutations selected from the group consisting of D265A, P329A, and combinations thereof numbered according to the EU numbering system can be made in the constant region of the polypeptides described herein. In one embodiment, mutations selected from the group consisting of L235A, L237A, and combinations thereof numbered according to the EU numbering system can be made in the constant region of the polypeptides described herein. In one embodiment, mutations selected from the group consisting of S267E, L328F, and combinations thereof numbered according to the EU numbering system can be made in the constant region of the polypeptides described herein. In one embodiment, mutations selected from the group consisting of S239D, I332E, optionally A330L, and combinations thereof numbered according to the EU numbering system can be made in the constant region of the polypeptides described herein. In one embodiment, mutations selected from the group consisting of L235V, F243L, R292P, Y300L, P396L, and combinations thereof numbered according to the EU numbering system can be made in the constant region of the polypeptides described herein. In one embodiment, mutations selected from the group consisting of S267E, L328F, and combinations thereof numbered according to the EU numbering system can be made in the constant region of the polypeptides described herein.

[0157] In one embodiment, the Fc region, Fc domain, or FcRn-binding fragment thereof described herein comprises the constant region of IgG1 having an N297Q or N297A amino acid substitution numbered according to the EU numbering system. In one embodiment, the Fc region, Fc domain, or FcRn-binding fragment thereof described herein comprises the constant region of IgG1 having a mutation selected from the group consisting of D265A, P329A, and combinations thereof numbered according to the EU numbering system. In one embodiment, the Fc region, Fc domain, or FcRn-binding fragment thereof described herein comprises the constant region of IgG1 having a mutation selected from the group consisting of L234A, L235A, and combinations thereof numbered according to the EU numbering system. In another embodiment, the Fc region, Fc domain, or FcRn-binding fragment thereof described herein comprises the constant region of IgG1 having a mutation selected from the group consisting of L234F, L235F, N297A, and combinations thereof numbered according to the EU numbering system. In one embodiment, the amino acid residues at positions corresponding to positions L234, L235, and D265 in the human IgG1 heavy chain, numbered according to the EU numbering system, in the constant region of the Fc region, Fc domain, or FcRn-binding fragment thereof described herein are not L, L, and D, respectively. This approach is described in detail in International Publication No. 14 / 108483, which is hereby incorporated by reference in its entirety. In one embodiment, the amino acids corresponding to positions L234, L235, and D265 in the human IgG1 heavy chain are F, E, and A, or A, A, and A, respectively, which are numbered according to the EU numbering system.

[0158] In one embodiment, the amino acids at positions 433, 434, and 436 of the heavy chain constant region according to the EU numbering system are K, F, and Y, respectively. In one embodiment, the amino acids at positions 252, 254, and 256 of the heavy chain constant region according to the EU numbering system are Y, T, and E, respectively. In one embodiment, the amino acids at positions 428 and 434 of the heavy chain constant region according to the EU numbering system are L and S, respectively. In one embodiment, the amino acids at positions 309, 311, and 434 of the heavy chain constant region according to the EU numbering system are D, H, and S, respectively.

[0159] In one embodiment, the polypeptide does not have the amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively.

[0160] In one embodiment, one or more amino acids selected from amino acid residues 329, 331, and 322, numbered according to the EU numbering system, in the constant region of the polypeptides described herein can be replaced with different amino acid residues, whereby the antibody has altered C1q binding and / or reduced or abolished complement-dependent cytotoxicity (CDC). This approach is described in more detail in U.S. Patent No. 6,194,551 (Idusogie et al.), which is hereby incorporated by reference in its entirety. In one embodiment, one or more amino acid residues within amino acid positions 231 - 238 in the N-terminal region of the CH2 domain of the polypeptides described herein are altered, thereby changing the ability of the antibody to fix complement, and these are numbered according to the EU numbering system. This approach is further described in International Publication No. 94 / 29351, which is hereby incorporated by reference in its entirety. In one embodiment, the Fc region or Fc domain of the polypeptides described herein is modified by mutating (e.g., introducing amino acid substitutions) one or more amino acids at the following positions: 238, 239, 248, 249, 252, 254, 255, 256, 258, 265, 267, 268, 269, 270, 272, 276, 278, 280, 283, 285, 286, 289, 290, 292, 293, 294, 295, 296, 298, 301, 303, 305, 307, 309, 312, 315, 320, 322, 324, 326, 327, 328, 329, 330, 331, 333, 334, 335, 337, 338, 340, 360, 373, 376, 378, 382, 388, 389, 398, 414, 416, 419, 430, 434, 435, 437, 438, or 439, and these are numbered according to the EU numbering system. This approach is further described in International Publication No. 00 / 42072, which is hereby incorporated by reference in its entirety.

[0161] In one embodiment, any of the constant region mutations or modifications described herein can be introduced into one or both of the heavy chain constant regions of a polypeptide described herein that has two heavy chain constant regions. In one embodiment, any of the constant region mutations or modifications described herein can be introduced into the heavy chain constant region of a polypeptide described herein that has one heavy chain constant region.

[0162] In one embodiment, the present disclosure provides a polypeptide comprising one, two, or three binding sites to human FcRn, which specifically binds to FcRn and functions as an antagonist.

[0163] In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region comprises the amino acid sequence of SEQ ID NO: 1. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 1. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region comprises the amino acid sequence of SEQ ID NO: 2. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 2. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region comprises the amino acid sequence of SEQ ID NO: 3. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 3.

[0164] In one embodiment, the FcRn binding molecule comprises a variant Fc region, the variant Fc region comprises two Fc domains, and the amino acid sequence of each of the Fc domains is independently selected from SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.

[0165] In certain embodiments, the variant Fc region is a heterodimer and the constituent Fc domains are different from each other. Methods for producing Fc heterodimers are known in the art (see, e.g., US8,216,805, which is incorporated herein by reference in its entirety). In one embodiment, the FcRn binding molecule consists of a variant Fc region, the variant Fc region consists of two Fc domains that form a heterodimer, and the amino acid sequence of each of the Fc domains is independently selected from SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3. In one embodiment, the FcRn binding molecule consists of or comprises a variant Fc region, the variant Fc region consists of or comprises two Fc domains that form a heterodimer, the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3. In one embodiment, the FcRn binding molecule consists of or comprises a variant Fc region, the variant Fc region consists of or comprises two Fc domains that form a heterodimer, the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 2, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3. In one embodiment, the FcRn binding molecule consists of or comprises a variant Fc region, the variant Fc region consists of or comprises two Fc domains that form a heterodimer, the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 3, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2.

[0166] In one embodiment, the FcRn binding molecule comprises a variant Fc region, the variant Fc region consists of or comprises two Fc domains that form a homodimer, and the amino acid sequence of each of the Fc domains consists of or comprises the amino acid sequence of SEQ ID NO: 1.

[0167] In one embodiment, the FcRn binding molecule comprises a variant Fc region, the variant Fc region consisting of or comprising two Fc domains that form a homodimer, and the amino acid sequence of each of the Fc domains consisting of or comprising the amino acid sequence of SEQ ID NO: 2.

[0168] In one embodiment, the FcRn binding molecule comprises a variant Fc region, the variant Fc region consisting of or comprising two Fc domains that form a homodimer, and the amino acid sequence of each of the Fc domains consisting of or comprising the amino acid sequence of SEQ ID NO: 3.

[0169] In one embodiment, the FcRn binding molecule comprises a variant Fc region, the variant Fc region comprising or consisting of efgartigimod (CAS Registry No. 1821402-21-4). As used herein, the term "efgartigimod" is interchangeable with "efgartigimod alpha". In some embodiments, efgartigimod is efgartigimod alpha-fcab.

[0170] In one embodiment, the variant Fc region is modified to promote heterodimerization. Such modifications are known in the art, and any suitable means for promoting heterodimerization can be used to generate the FcRn / antigen-binding molecules described herein. In some embodiments, the variant Fc region comprises one or more mutations of amino acid residues that form the interface of the CH3 domain of the Fc domain. In some embodiments, the variant Fc region comprises a knob-into-hole mutation (see, e.g., WO 2006 / 028936, which is incorporated herein by reference in its entirety). Mis-pairing of Ig heavy chains is reduced in this technique by mutating selected amino acids that form the interface of the CH3 domain in IgG. At positions within the CH3 domain where the two heavy chains interact directly, one or more amino acids with small side chains (holes) are introduced into the sequence of one heavy chain, and one or more amino acids with large side chains (knobs) are introduced into the corresponding interacting residue position(s) on the other heavy chain. The Fc domain of the Fc region can be composed of immunoglobulin chains of the same subclass (e.g., IgG1 or IgG3) or different subclasses (e.g., IgG1 and IgG3, or IgG3 and IgG4). Such an interface between the CH3 domain of the first Fc domain and the CH3 domain of the second Fc domain results in correct Fc association of an FcRn / antigen-binding molecule comprising a variant IgG Fc region and only one antigen-binding domain linked to the variant IgG Fc region, wherein the antigen-binding domain specifically binds to a human antigen, the variant IgG Fc region comprises or consists of a first Fc domain and a second Fc domain that form a dimer, and the variant Fc region comprises one or more mutations of amino acid residues that form the interface of the CH3 domain of the Fc domain.

[0171] In some embodiments, the variant Fc region comprises or consists of two Fc domains, and one of the Fc domains comprises amino acid W at EU position 366. In some embodiments, the variant Fc region comprises or consists of two Fc domains, and one of the Fc domains comprises amino acids S, A, and V at EU positions 366, 368, and 407, respectively. In some embodiments, the variant Fc region comprises or consists of two Fc domains, one Fc domain comprises amino acid W at EU position 366, and the other Fc domain comprises amino acids S, A, and V at EU positions 366, 368, and 407, respectively.

[0172] In some embodiments, the variant Fc region comprises or consists of two Fc domains, wherein one Fc domain comprises amino acids E and D at EU positions 370 and 409, respectively, and the other Fc domain comprises amino acid K at EU positions 357 and 399. In some embodiments, the variant Fc region comprises or consists of two Fc domains, wherein one Fc domain comprises H and A at EU positions 364 and 405, respectively, and the other Fc domain comprises amino acids T and F at EU positions 349 and 394, respectively. In some embodiments, the variant Fc region comprises or consists of two Fc domains, wherein one Fc domain comprises amino acids V, Y, A, and V at EU positions 350, 351, 405, and 407, respectively, and the other Fc domain comprises amino acids V, L, L, and W at EU positions 350, 366, 392, and 394, respectively. In some embodiments, the variant Fc region comprises or consists of two Fc domains, wherein one Fc domain comprises amino acids D, M, and A at EU positions 360, 399, and 407, respectively, and the other Fc domain comprises amino acids R, R, V, and V at EU positions 345, 347, 366, and 409, respectively. In some embodiments, the variant Fc region comprises or consists of two Fc domains, wherein one Fc domain comprises amino acid D at EU positions 409 and 392, and the other Fc domain comprises amino acid K at EU positions 399 and 356. In some embodiments, the variant Fc region comprises or consists of two Fc domains, wherein one Fc domain comprises amino acids E, W, and C at EU positions 360, 409, and 349, respectively, and the other Fc domain comprises amino acids R, V, T, and C at EU positions 347, 399, 405, and 354, respectively.In some embodiments, the variant Fc region comprises or consists of two Fc domains, wherein one Fc domain comprises amino acids E and W at EU positions 370 and 409, respectively, and the other Fc domain comprises amino acids N, V, and T at EU positions 357, 399, and 405, respectively.

[0173] In one embodiment, the FcRn-binding molecule consists of a variant Fc region, the variant Fc region comprising or consisting of two Fc domains that form a heterodimer, wherein the amino acid sequence of the first Fc domain is selected from the amino acid sequences comprising or consisting of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, and / or the amino acid sequence of the second Fc domain is selected from the amino acid sequences comprising or consisting of SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9. In one embodiment, the FcRn-binding molecule consists of a variant Fc region, the variant Fc region comprising or consisting of two Fc domains that form a heterodimer, wherein the amino acid sequence of the first Fc domain is selected from the amino acid sequences comprising or consisting of SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, and / or the amino acid sequence of the second Fc domain is selected from the amino acid sequences comprising or consisting of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6. In one embodiment, the FcRn-binding molecule consists of a variant Fc region, the variant Fc region comprising or consisting of two Fc domains that form a heterodimer, wherein the amino acid sequence of the first Fc domain comprises or consists of SEQ ID NO: 4, and the amino acid sequence of the second Fc domain comprises or consists of SEQ ID NO: 7. In one embodiment, the FcRn-binding molecule consists of a variant Fc region, the variant Fc region comprising or consisting of two Fc domains that form a heterodimer, wherein the amino acid sequence of the first Fc domain comprises or consists of SEQ ID NO: 5, and the amino acid sequence of the second Fc domain comprises or consists of SEQ ID NO: 8. In one embodiment, the FcRn-binding molecule consists of a variant Fc region, the variant Fc region comprising or consisting of two Fc domains that form a heterodimer, wherein the amino acid sequence of the first Fc domain comprises or consists of SEQ ID NO: 6, and the amino acid sequence of the second Fc domain comprises or consists of SEQ ID NO: 9. In some embodiments, the FcRn-binding molecule is an FcRn antagonist. Table 1. Amino acid sequences of variant Fc regions [Table 1]

[0174] In some embodiments, the variant Fc region comprises a first Fc domain comprising amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively, and a second Fc domain comprising amino acids K and F at EU positions 433 and 434, respectively. In some embodiments, the first Fc domain comprises the amino acid sequence of SEQ ID NO: 1. In some embodiments, the first Fc domain comprises the amino acid sequence of SEQ ID NO: 2. In some embodiments, the first Fc domain comprises the amino acid sequence of SEQ ID NO: 3.

[0175] In some embodiments, the variant Fc region comprises a first Fc domain comprising amino acids Y, T, E, W, K, and F at EU positions 252, 254, 256, 366, 433, and 434, respectively, and a second Fc domain comprising amino acids S, A, V, K, and F at EU positions 366, 368, 407, 433, and 434, respectively. In some embodiments, the first Fc domain comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the first Fc domain comprises the amino acid sequence of SEQ ID NO: 5. In some embodiments, the first Fc domain comprises the amino acid sequence of SEQ ID NO: 6.

[0176] In some embodiments, the variant Fc region comprises a first Fc domain comprising amino acids Y, T, E, S, A, V, K, and F at EU positions 252, 254, 256, 366, 368, 407, 433, and 434, respectively, and a second Fc domain comprising amino acids W, K, and F at EU positions 366, 433, and 434, respectively. In some embodiments, the first Fc domain comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the first Fc domain comprises the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first Fc domain comprises the amino acid sequence of SEQ ID NO: 9.

[0177] In one embodiment, the anti-FcRn antibody is rozanolixizumab (UCB7665), nipocalimab (M281), orilanolimab (ALXN1830 / SYNT001), or batoclimab (IMVT-1401 / RVT1401 / HBM9161).

[0178] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of immunoglobulin to FcRn is nipocalimab, also known as M281. Nipocalimab is a full-length "Fc dead" IgG1 monoclonal antibody. Nipocalimab is being administered as an intravenous infusion in Phase 2 / 3 clinical trials for the treatment of myasthenia gravis (MG) and warm antibody autoimmune hemolytic anemia (WAIHA), and in Phase 2 clinical trials for the treatment of fetal and neonatal hemolytic disease (HDFN), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS). Nipocalimab contains the light chain (SEQ ID NO: 128) and heavy chain (SEQ ID NO: 129) sequences shown in Table 2 below (the VL of SEQ ID NO: 128 and the VH of SEQ ID NO: 129 are underlined). Table 2. Heavy and Light Chain Sequences of Nipocalimab [Table 2]

[0179] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of immunoglobulin to FcRn is rozanolixizumab, also known as UCB 7665. Rozanolixizumab is a full-length humanized IgG4 monoclonal antibody. Rozanolixizumab is being administered as a subcutaneous injection in clinical trials for MG, immune thrombocytopenic purpura (ITP), chronic inflammatory demyelinating polyneuropathy (CIDP), autoimmune encephalitis (AIE), and myelin oligodendrocyte glycoprotein-related disease (MOG-AD). Rozanolixizumab contains the light chain (SEQ ID NO: 130) and heavy chain (SEQ ID NO: 131) sequences shown in Table 3 below (the VL of SEQ ID NO: 130 and the VH of SEQ ID NO: 131 are underlined). Table 3. Heavy and Light Chain Sequences of Rozanolixizumab

Table 3

[0180] In one embodiment, an antibody that specifically binds to FcRn and inhibits the binding of the Fc region of an immunoglobulin to FcRn is orilanolimab, also known as SYNT001 / ALXN1830. Orilanolimab is another full-length humanized IgG4 monoclonal antibody. Orilanolimab is being administered as an intravenous infusion in Phase 2 clinical trials for the treatment of WAIHA and pemphigus. Orilanolimab comprises the light chain (SEQ ID NO: 132) and heavy chain (SEQ ID NO: 133) sequences set forth in Table 4 below (VL of SEQ ID NO: 132 and VH of SEQ ID NO: 133 are underlined). Table 4. Heavy and Light Chain Sequences of Orilanolimab

Table 4

[0181] In one embodiment, an antibody that specifically binds to FcRn and inhibits the binding of the Fc region of an immunoglobulin to FcRn is batoclimab, also known as IMVT1401 / RVT1401 / HBM9161. Batoclimab is another full-length "Fc dead" IgG1 monoclonal antibody. Batoclimab is being administered as a subcutaneous injection in Phase 2 clinical trials for the treatment of MG, ITP, Graves' ophthalmopathy, thyroid ophthalmopathy, and neuromyelitis optica spectrum disorder (NMOSD). Batoclimab comprises the light chain (SEQ ID NO: 134) and heavy chain (SEQ ID NO: 135) sequences set forth in Table 5 below (VL of SEQ ID NO: 134 and VH of SEQ ID NO: 135 are underlined). Table 5. Heavy and Light Chain Sequences of Batoclimab

Table 5

[0182] Antigen-binding domain In one aspect, an antigen-binding domain is provided by the present disclosure. In some embodiments, the FcRn / antigen-binding molecules disclosed herein comprise one or more FcRn-binding molecules in combination with one or more antigen-binding domains. In some embodiments, the FcRn / antigen-binding molecules disclosed herein comprise one or more Fc regions or FcRn-binding fragments thereof in combination with one or more antigen-binding domains. In some embodiments, the antigen-binding domain is a polypeptide derived from an antibody, and the antibody includes, but is not limited to, sdAb (e.g., VHH fragment), Fab fragment, scFv, VH, or VL. In some embodiments, the antigen-binding domain is a synthetic antigen-binding protein or an antibody mimetic protein, and the synthetic antigen-binding protein or antibody mimetic protein includes, but is not limited to, anticalin or DARPin.

[0183] In some embodiments, the antigen-binding domain further comprises one or more amino acids added at its C-terminus. In some embodiments, the antigen-binding domain further comprises one or more amino acids added at the C-terminus, and the one or more amino acids are selected from A, AG, GG, and PP. In some embodiments, the C-terminus of VHH has the amino acid sequence VTVSS (SEQ ID NO: 296). In some embodiments, the C-terminus of VHH consists of the amino acid sequence VTVSS (SEQ ID NO: 296).

[0184] The antigen-binding domain can bind to any human antigen, such as a protein or a fragment thereof that is normally expressed by a human. In some embodiments, the human antigen is selected from HSA or IgE.

[0185] In some embodiments, the antigen-binding domain specifically binds to HSA. In some embodiments, the antigen-binding domain specifically binds to HSA and is selected from Fab fragments, scFv, sdAb, HSA, and HSA-binding fragments thereof. In some embodiments, the antigen-binding domain specifically binds to HSA and is an sdAb, such as a VHH fragment. In some embodiments, HSA comprises an amino acid sequence that is at least 95% identical to the amino acid sequence provided in GenBank accession number AAA98797.1. In some embodiments, HSA comprises the amino acid sequence provided in GenBank accession number AAA98797.1.

[0186] In some embodiments, the antigen-binding domain is a VHH fragment, and the VHH fragment comprises a CDR1 amino acid sequence, a CDR2 amino acid sequence, and a CDR3 amino acid sequence of a VHH fragment comprising an amino acid sequence selected from SEQ ID NOs: 43-74, 84-90, and 120-127.

[0187] In some embodiments, the antigen-binding domain is a VHH fragment, the VHH fragment comprising or consisting of a combination of CDR1, CDR2, and CDR3, wherein 1, 2, 3, 4, or 5 amino acids are SEQ ID NO: 10, 11, and 12; 13, 11, and 12; 14, 11, and 12; 15, 11, and 12; 16, 11, and 12; 17, 11, and 12; 10, 18, and 12; 10, 19, and 12; 10, 20, and 12; 10, 21, and 12; 10, 22, and 12; 10, 23, and 12; 10, 24, and 12; 10, 25, and 12; 10, 26, and 12; 10, 27, and 12; 10, 28, and 12; 10, 29, and 12; 10, 30, and 12; 10, 31, and 12; 10, 32, and 12; 10, 33, and 12; 10, 11, and 34; 10, 11, and 35; 10, 11, and 36; 10, 11, and 37; 10, 11, and 38; 10, 11, and 39; 10, 11, and 40; 15, 11, and 36; 15, 21, and 12; 10, 41, and 12; 10, 20, and 36; 111, 11, and 12; 112, 11, and 12; 10, 113, and 12; 10, 114, and 12; 10, 11, and 115; 10, 11, and 116; 10, 11, and 117; 118, 11, and 119; 75, 76, and 77; 75, 76, and 78; 75, 76, and 79; 75, 76, and 80; 75, 76, and 81; 75, 76, and 82; 75, 76, and 83; 182, 11, and 12; 14, 27, and 12; 14, 11, and 34; 14, 11, and 35; 14, 11, and 37; 183, 11, and 36; 16, 27, and 12; 16, 11, and 34; 16, 11, and 35; 16, 11, and 37; 184, 11, and 36; 10, 27, and 34; 10, 27, and 35; 10, 27, and 37; 15, 27, and 36; 185, 11, and 12; 118, 11, and 12; 186, 11, and 12; 10, 187, and 12; 10, 188, and 12; 10, 189, and 12; 10, 190, and 12; 10, 191, and 12; 10, 192, and 12; 10, 193, and 12; 10, 194, and 12; 10, 195, and 12; 10, 196, and 12; 10, 197, and 12; 10, 198, and 12; 10, 199, and 12;Differ in at least one of the amino acid sequences selected from 10, 200, and 12; 10, 201, and 12; 10, 11, and 119; 10, 11, and 202; and 10, 11, and 203.;

[0188] In some embodiments, the antigen-binding domain is a VHH fragment, and the VHH fragment has the sequences of SEQ ID NOs: 10, 11, and 12; 13, 11, and 12; 14, 11, and 12; 15, 11, and 12; 16, 11, and 12; 17, 11, and 12; 10, 18, and 12; 10, 19, and 12; 10, 20, and 12; 10, 21, and 12; 10, 22, and 12; 10, 23, and 12; 10, 24, and 12; 10, 25, and 12; 10, 26, and 12; 10, 27, and 12; 10, 28, and 12; 10, 29, and 12; 10, 30, and 12; 10, 31, and 12; 10, 32, and 12; 10, 33, and 12; 10, 11, and 34; 10, 11, and 35; 10, 11, and 36; 10, 11, and 37; 10, 11, and 38; 10, 11, and 39; 10, 11, and 40; 15, 11, and 36; 15, 21, and 12; 10, 41, and 12; 10, 20, and 36; 111, 11, and 12; 112, 11, and 12; 10, 113, and 12; 10, 114, and 12; 10, 11, and 115; 10, 11, and 116; 10, 11, and 117; 118, 11, and 119; 75, 76, and 77; 75, 76, and 78; 75, 76, and 79; 75, 76, and 80; 75, 76, and 81; 75, 76, and 82; 75, 76, and 83; 182, 11, and 12; 14, 27, and 12; 14, 11, and 34; 14, 11, and 35; 14, 11, and 37; 183, 11, and 36; 16, 27, and 12; 16, 11, and 34; 16, 11, and 35; 16, 11, and 37; 184, 11, and 36; 10, 27, and 34; 10, 27, and 35; 10, 27, and 37; 15, 27, and 36; 185, 11, and 12; 118, 11, and 12; 186, 11, and 12; 10, 187, and 12; 10, 188, and 12; 10, 189, and 12; 10, 190, and 12; 10, 191, and 12; 10, 192, and 12; 10, 193, and 12; 10, 194, and 12; 10, 195, and 12; 10, 196, and 12; 10, 197, and 12; 10, 198, and 12; 10, 199, and 12; 10, 200, and 12; 10, 201, and 12; 10, 11, and 119; 10, 11, and 202;comprising or consisting of a combination of CDR1, CDR2, and CDR3 selected from 10, 11, and 203, wherein one or more amino acids within one or more CDRs are substituted with alanine or histidine.;

[0189] In some embodiments, the antigen-binding domain is a VHH fragment, and the VHH fragment has the sequences of SEQ ID NOs: 10, 11, and 12; 13, 11, and 12; 14, 11, and 12; 15, 11, and 12; 16, 11, and 12; 17, 11, and 12; 10, 18, and 12; 10, 19, and 12; 10, 20, and 12; 10, 21, and 12; 10, 22, and 12; 10, 23, and 12; 10, 24, and 12; 10, 25, and 12; 10, 26, and 12; 10, 27, and 12; 10, 28, and 12; 10, 29, and 12; 10, 30, and 12; 10, 31, and 12; 10, 32, and 12; 10, 33, and 12; 10, 11, and 34; 10, 11, and 35; 10, 11, and 36; 10, 11, and 37; 10, 11, and 38; 10, 11, and 39; 10, 11, and 40; 15, 11, and 36; 15, 21, and 12; 10, 41, and 12; 10, 20, and 36; 111, 11, and 12; 112, 11, and 12; 10, 113, and 12; 10, 114, and 12; 10, 11, and 115; 10, 11, and 116; 10, 11, and 117; 118, 11, and 119; 75, 76, and 77; 75, 76, and 78; 75, 76, and 79; 75, 76, and 80; 75, 76, and 81; 75, 76, and 82; 75, 76, and 83; 182, 11, and 12; 14, 27, and 12; 14, 11, and 34; 14, 11, and 35; 14, 11, and 37; 183, 11, and 36; 16, 27, and 12; 16, 11, and 34; 16, 11, and 35; 16, 11, and 37; 184, 11, and 36; 10, 27, and 34; 10, 27, and 35; 10, 27, and 37; 15, 27, and 36; 185, 11, and 12; 118, 11, and 12; 186, 11, and 12; 10, 187, and 12; 10, 188, and 12; 10, 189, and 12; 10, 190, and 12; 10, 191, and 12; 10, 192, and 12; 10, 193, and 12; 10, 194, and 12; 10, 195, and 12; 10, 196, and 12; 10, 197, and 12; 10, 198, and 12; 10, 199, and 12; 10, 200, and 12; 10, 201, and 12; 10, 11, and 119; 10, 11, and 202;Comprises or consists of a combination of CDR1, CDR2, and CDR3 selected from 10, 11, and 203;

[0190] In some embodiments, the antigen-binding domain is a VHH fragment, and the VHH fragment comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to an amino acid sequence selected from SEQ ID NOs: 42-74, 84-90, 120-127, and 204-249. In some embodiments, the antigen-binding domain is a VHH fragment, and the VHH fragment comprises or consists of an amino acid sequence selected from SEQ ID NOs: 42-74, 84-90, 120-127, and 204-249.

[0191] In some embodiments, the antigen-binding domain specifically binds to IgE. In some embodiments, the antigen-binding domain specifically binds to IgE and is selected from Fab, scFv, and sdAb. In some embodiments, the antigen-binding domain specifically binds to IgE and is a Fab or scFv.

[0192] In some embodiments, the antigen-binding domain is a Fab or scFv, and the Fab or scFv comprises the HCDR1 amino acid sequence, HCDR2 amino acid sequence, and HCDR3 amino acid sequence of the VH comprising the amino acid sequence of SEQ ID NO: 108, and the LCDR1 amino acid sequence, LCDR2 amino acid sequence, and LCDR3 amino acid sequence of the VL comprising the amino acid sequence of SEQ ID NO: 107.

[0193] In some embodiments, the antigen-binding domain is a Fab or scFv, the Fab or scFv comprises a combination of VHCDR1, VHCDR2, VHCDR3, VLCDR1, VLCDR2, and VLCDR3, and 1, 2, 3, 4, or 5 amino acids differ in at least one of the amino acid sequences selected from SEQ ID NOs: 101, 102, 103, 104, 105, and 106. In some embodiments, the antigen-binding domain is a Fab or scFv, the Fab or scFv comprises a combination of VHCDR1, VHCDR2, VHCDR3, VLCDR1, VLCDR2, and VLCDR3 selected from SEQ ID NOs: 101, 102, 103, 104, 105, and 106.

[0194] In some embodiments, the antigen-binding domain is a Fab or scFv, the Fab or scFv consists of a combination of VHCDR1, VHCDR2, VHCDR3, VLCDR1, VLCDR2, and VLCDR3, and 1, 2, 3, 4, or 5 amino acids differ in at least one of the amino acid sequences selected from SEQ ID NOs: 101, 102, 103, 104, 105, and 106. In some embodiments, the antigen-binding domain is a Fab or scFv, the Fab or scFv consists of a combination of VHCDR1, VHCDR2, VHCDR3, VLCDR1, VLCDR2, and VLCDR3 selected from SEQ ID NOs: 101, 102, 103, 104, 105, and 106.

[0195] In some embodiments, the antigen-binding domain is a Fab or scFv comprising VH and VL, VH comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 108, and VL comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 107. In some embodiments, the antigen-binding domain is a Fab or scFv comprising VH and VL, VH comprises the amino acid sequence of SEQ ID NO: 108, and VL comprises the amino acid sequence of SEQ ID NO: 107.

[0196] In some embodiments, the antigen-binding domain is a Fab or scFv comprising VH and VL, wherein VH consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence selected from SEQ ID NO: 108, and VL consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence selected from SEQ ID NO: 107. In some embodiments, the antigen-binding domain is a Fab or scFv comprising VH and VL, wherein VH consists of the amino acid sequence of SEQ ID NO: 108, and VL consists of the amino acid sequence of SEQ ID NO: 107.

[0197] Linker The antigen-binding domain can be linked to the N-terminus or C-terminus of an FcRn-binding molecule (e.g., an Fc domain). Alternatively, the antigen-binding domain can be linked at a position other than the N-terminus or C-terminus of the FcRn-binding molecule (e.g., an Fc domain).

[0198] In some embodiments, the antigen-binding domain can be non-covalently linked to the FcRn-binding molecule. In some embodiments, the antigen-binding domain can be covalently linked to the FcRn-binding molecule.

[0199] In some embodiments, the antigen-binding domain can be directly linked (e.g., fused) to the N-terminus or C-terminus of the FcRn-binding molecule. In some embodiments, the antigen-binding domain is linked to the N-terminus or C-terminus of the FcRn-binding molecule via a linker. In some embodiments, the linker is a non-cleavable linker.

[0200] In some embodiments, the antigen-binding domain can be directly linked (e.g., fused) to the N-terminus or C-terminus of the Fc domain. In some embodiments, the antigen-binding domain is linked to the N-terminus or C-terminus of the Fc domain via a linker. In some embodiments, the linker is a non-cleavable linker. As used herein, the term "non-cleavable linker" refers to a linker that is not readily cleaved by one or more of a given enzyme, chemical agent, or light irradiation. In some embodiments, the enzyme is a protease.

[0201] In some embodiments, the linker is a synthetic compound linker, such as a chemical cross-linking agent. Non-limiting examples of suitable commercially available cross-linking agents include N-hydroxysuccinimide (NHS), disuccinimidyl suberate (DSS), bis(sulfosuccinimidyl) suberate (BS3), dithiobis(succinimidyl propionate) (DSP), dithiobis(sulfosuccinimidyl propionate) (DTSSP), ethylene glycol bis(succinimidyl succinate) (EGS), ethylene glycol bis(sulfosuccinimidyl succinate) (sulfo-EGS), disuccinimidyl tartrate (DST), disulfosuccinimidyl tartrate (sulfo-DST), bis[2-(succinimidooxycarbonyloxy)ethyl] sulfone (BSOCOES), and bis[2-(sulfosuccinimidooxycarbonyloxy)ethyl] sulfone (sulfo-BSOCOES).

[0202] As described above, the Fc domain disclosed herein may include a portion of the hinge region. Thus, the antigen-binding domain may be linked to the N-terminus of the Fc domain via this hinge region. In some embodiments, one or more amino acids are included between the C-terminus of the antigen-binding domain and the N-terminus of the Fc domain. In some embodiments, the one or more amino acids included between the C-terminus of the antigen-binding domain and the N-terminus of the Fc domain are amino acids of the native hinge region. In some embodiments, the C-terminus of the antigen-binding domain is fused to the N-terminus of the Fc domain via a hinge region or a portion thereof. In some embodiments, the hinge region is the IgG hinge region, e.g., the human IgG hinge region.

[0203] In some embodiments, the linker is a peptide linker. Examples of peptide linkers are well known, and those skilled in the art can select a suitable peptide linker for use in the linkage of an antigen-binding domain to an FcRn-binding molecule, e.g., an Fc domain.

[0204] The peptide linker can be of any length. In some embodiments, the length and amino acid composition of the linker peptide sequence can be optimized to vary the orientation and / or proximity of the polypeptide domains to each other to achieve the desired activity of the FcRn / antigen-binding molecule. In some embodiments, the peptide linker is about 1 to about 100 amino acids in length, about 8 to about 40 amino acids in length, or about 15 amino acids to about 25 amino acids in length. In some embodiments, the peptide linker is 1 to 100 amino acids in length, 8 to 40 amino acids in length, or 15 to 25 amino acids in length. In some embodiments, the peptide linker is about 8 amino acids in length, about 9 amino acids in length, about 10 amino acids in length, about 11 amino acids in length, about 12 amino acids in length, about 13 amino acids in length, about 14 amino acids in length, about 15 amino acids in length, about 16 amino acids in length, about 17 amino acids in length, about 18 amino acids in length, about 19 amino acids in length, about 20 amino acids in length, about 21 amino acids in length, about 22 amino acids in length, about 23 amino acids in length, about 24 amino acids in length, about 25 amino acids in length, about 26 amino acids in length, about 27 amino acids in length, about 28 amino acids in length, about 29 amino acids in length, about 30 amino acids in length, about 31 amino acids in length, about 32 amino acids in length, about 33 amino acids in length, about 34 amino acids in length, about 35 amino acids in length, about 36 amino acids in length, about 37 amino acids in length, about 38 amino acids in length, about 39 amino acids in length, or about 40 amino acids in length. In some embodiments, the peptide linker is 8 amino acids in length, 9 amino acids in length, 10 amino acids in length, 11 amino acids in length, 12 amino acids in length, 13 amino acids in length, 14 amino acids in length, 15 amino acids in length, 16 amino acids in length, 17 amino acids in length, 18 amino acids in length, 19 amino acids in length, 20 amino acids in length, 21 amino acids in length, 22 amino acids in length, 23 amino acids in length, 24 amino acids in length, 25 amino acids in length, 26 amino acids in length, 27 amino acids in length, 28 amino acids in length, 29 amino acids in length, 30 amino acids in length, 31 amino acids in length, 32 amino acids in length, 33 amino acids in length, 34 amino acids in length, 35 amino acids in length, 36 amino acids in length, 37 amino acids in length, 38 amino acids in length, 39 amino acids in length, or 40 amino acids in length.

[0205] In some embodiments, the peptide linker contains only glycine residues and / or serine residues (e.g., glycine-serine linker or GS linker). Examples of such peptide linkers include Gly(x)Ser (where x is from 0 to 6), or Ser Gly(x) (where x is from 0 to 6), (Gly Gly Gly Gly Ser)n (where n is an integer of 1 or more), and (Ser Gly Gly Gly Gly)n (where n is an integer of 1 or more). In some embodiments, the peptide linker comprises an amino acid sequence selected from the group consisting of (GGGGS)n and (SGGGG)n, where n is from 1 to 8. In some embodiments, the linker peptide is modified such that the amino acid sequence GSG (which occurs at the junction of conventional Gly / Ser linker peptide repeats) is absent. For example, in some embodiments, the peptide linker comprises an amino acid sequence selected from the group consisting of (GGGXX)nGGGGS and GGGGS(XGGGS)n (where X is any amino acid that can be inserted into the sequence and does not result in a polypeptide containing the sequence GSG, and n is from 0 to 4). In some embodiments, the sequence of the linker peptide is (GGGX1X2)nGGGGS, where X1 is P, X2 is S, and n is from 0 to 4. In some other embodiments, the sequence of the linker peptide is (GGGX1X2)nGGGGS, where X1 is G, X2 is Q, and n is from 0 to 4. In some other embodiments, the sequence of the linker peptide is (GGGX1X2)nGGGGS, where X1 is G, X2 is A, and n is from 0 to 4. In yet other embodiments, the sequence of the linker peptide is GGGGS(XGGGS)n, where X is P, and n is from 0 to 4. In some embodiments, the linker peptide of the present disclosure comprises or consists of the amino acid sequence (GGGG A)2GGGGS. In some embodiments, the linker peptide comprises or consists of the amino acid sequence (GGGGQ)2GGGGS. In another embodiment, the linker peptide comprises or consists of the amino acid sequence (GGGPS)2GGGGS. In another embodiment, the linker peptide comprises or consists of the amino acid sequence GGGGS(PGGGS)2.In yet another embodiment, the linker peptide comprises or consists of the amino acid sequence GSGGS or SGGSGS. In some embodiments, the linker peptide comprises or consists of the amino acid sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 136), GGGGSGGGGS (SEQ ID NO: 180), or GGGGSGGGGSGGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 181).

[0206] In some embodiments, the peptide linker is a GS linker that is about 20 or about 30 amino acids in length. In some embodiments, the peptide linker is a GS linker that is 20 or 30 amino acids in length.

[0207] Heavy chain molecule In some embodiments, the FcRn / antigen-binding molecule can comprise the first heavy chain described herein. In some embodiments, the first heavy chain comprises an Fc domain and an antigen-binding domain linked by a linker. In some embodiments, the FcRn / antigen-binding molecule can further comprise the second heavy chain described herein. In some embodiments, the second heavy chain comprises an Fc domain and an antigen-binding domain linked by a linker. In some embodiments, the second heavy chain comprises an Fc domain. In some embodiments, the first and second heavy chains are the same. In some embodiments, the first and second heavy chains are different.

[0208] In some embodiments, the first and second heavy chains have the same Fc domain. In some embodiments, the first and second heavy chains have different Fc domains. In some embodiments, the first heavy chain comprises an Fc domain and an antigen-binding domain, and the second heavy chain comprises an Fc but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain comprises an Fc domain and an antigen-binding domain, and the second heavy chain comprises an Fc domain but does not comprise an antigen-binding domain or a linker. In some embodiments, the first heavy chain comprises an Fc domain, an antigen-binding domain, and a linker, and the second heavy chain comprises an Fc domain but does not comprise an antigen-binding domain or a linker.

[0209] In some embodiments, the antigen-binding domain is linked to the N-terminus of the Fc domain. In some embodiments, the antigen-binding domain is linked to the C-terminus of the Fc domain. In some embodiments, the antigen-binding domain is linked to a position other than the N-terminus or C-terminus of the Fc domain.

[0210] In some embodiments, the antigen-binding domain is fused to the N-terminus of the Fc domain. In some embodiments, the antigen-binding domain is fused to the C-terminus of the Fc domain. In some embodiments, the antigen-binding domain is fused to a position other than the N-terminus or C-terminus of the Fc domain.

[0211] In some embodiments, the antigen-binding domain is linked to the N-terminus of the Fc domain by a linker. In some embodiments, the antigen-binding domain is linked to the C-terminus of the Fc domain by a linker. In some embodiments, the antigen-binding domain is linked to a position other than the N-terminus or C-terminus of the Fc domain by a linker.

[0212] In some embodiments, the antigen-binding domain is fused to the N-terminus of the Fc domain by a peptide linker. In some embodiments, the antigen-binding domain is fused to the C-terminus of the Fc domain by a peptide linker. In some embodiments, the antigen-binding domain is fused to a position other than the N-terminus or C-terminus of the Fc domain by a peptide linker.

[0213] In some embodiments, the Fc domain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 1-9. In some embodiments, the Fc domain consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 1-9.

[0214] In some embodiments, the Fc domain comprises an amino acid sequence of any one of SEQ ID NOs: 1-9. In some embodiments, the Fc domain consists of an amino acid sequence of any one of SEQ ID NOs: 1-9.

[0215] In some embodiments, the first and second heavy chains comprise the same Fc domain. In some embodiments, both the first and second heavy chains comprise an Fc domain that comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to an amino acid sequence of any one of SEQ ID NOs: 1-3. In some embodiments, both the first and second heavy chains comprise an Fc domain consisting of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to an amino acid sequence of any one of SEQ ID NOs: 1-3. In some embodiments, both the first and second heavy chains comprise an Fc domain that comprises an amino acid sequence of any one of SEQ ID NOs: 1-3. In some embodiments, both the first and second heavy chains comprise an Fc domain consisting of an amino acid sequence of any one of SEQ ID NOs: 1-3.

[0216] In some embodiments, the first and second heavy chains comprise different Fc domains. In some embodiments, the first heavy chain comprises an Fc domain comprising an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 4-6, and the second heavy chain comprises an Fc domain comprising an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 7-9. In some embodiments, the first heavy chain comprises an Fc domain consisting of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 4-6, and the second heavy chain comprises an Fc domain consisting of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 7-9. In some embodiments, the first heavy chain comprises an Fc domain comprising an amino acid sequence of any one of SEQ ID NOs: 4-6, and the second heavy chain comprises an Fc domain comprising an amino acid sequence of any one of SEQ ID NOs: 7-9. In some embodiments, when the first heavy chain comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the second heavy chain comprises an Fc domain comprising SEQ ID NO: 7 or a variant thereof. In some embodiments, when the first heavy chain comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 5 or a variant thereof, the second heavy chain comprises an Fc domain comprising SEQ ID NO: 8 or a variant thereof. In some embodiments, when the first heavy chain comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 6 or a variant thereof, the second heavy chain comprises an Fc domain comprising SEQ ID NO: 9 or a variant thereof.

[0217] In some embodiments, the first and second heavy chains further comprise a peptide linker. In some embodiments, the first and second heavy chains further comprise the same peptide linker. In some embodiments, the first and second heavy chains further comprise different peptide linkers. In some embodiments, the first heavy chain comprises an Fc domain, a peptide linker, and an antigen-binding domain, and the second heavy chain comprises an Fc domain but does not comprise a peptide linker or an antigen-binding domain. The peptide linker encoded by the first and heavy chains can be any of those described herein. In some embodiments, the linker comprises the amino acid sequence of SEQ ID NO: 136, 180, or 181.

[0218] In some embodiments, the FcRn / antigen-binding molecule comprises an amino acid sequence selected from Table 6 or a variant thereof.

Table 6

[0219] In some embodiments, the FcRn / antigen-binding molecule comprises, or consists of, an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 137-176 and 250-295. In some embodiments, the FcRn / antigen-binding molecule comprises, or consists of, any one of the amino acid sequences of SEQ ID NOs: 137-176 and 250-295.

[0220] In some embodiments, the FcRn / antigen-binding molecule comprises any one of the amino acid sequences of SEQ ID NOs: 137-176 and 250-295 or a variant thereof, and one or more amino acids added at the C-terminus. In some embodiments, the FcRn / antigen-binding molecule comprises any one of the amino acid sequences of SEQ ID NOs: 137-176 and 250-295 or a variant thereof, and one or more amino acids added at the C-terminus, and the one or more amino acids are selected from A, AG, GG, and PP.

[0221] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises, or consists of, an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 137-176 and 250-295, and the second heavy chain of the FcRn / antigen-binding molecule does not contain an antigen-binding domain. In some embodiments, the second heavy chain of the FcRn / antigen-binding molecule contains an Fc domain but does not contain an antigen-binding domain. Optionally, the second heavy chain of the FcRn / antigen-binding molecule comprises, or consists of, an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 8.

[0222] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises or consists of any one amino acid sequence among SEQ ID NOs: 137-176 and 250-295, and the second heavy chain of the FcRn / antigen-binding molecule does not contain an antigen-binding domain. In some embodiments, the second heavy chain of the FcRn / antigen-binding molecule contains an Fc domain but does not contain an antigen-binding domain. Optionally, the second heavy chain of the FcRn / antigen-binding molecule comprises or consists of the amino acid sequence of SEQ ID NO: 8.

[0223] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 137, and the second heavy chain of the FcRn / antigen-binding molecule contains an Fc domain that comprises the amino acid sequence of SEQ ID NO: 8 but does not contain an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 137, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0224] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 137, and the second heavy chain of the FcRn / antigen-binding molecule contains an Fc domain that comprises the amino acid sequence of SEQ ID NO: 8 but does not contain an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 137, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0225] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 138, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 138, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0226] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 138, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 138, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0227] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 139, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 139, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0228] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 139, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 139, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0229] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 140, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 140, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0230] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 140, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 140, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0231] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 141, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 141, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0232] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 141, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 141, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0233] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 142, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 142, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0234] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 142, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 142, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0235] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 143, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 143, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0236] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 143, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 143, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0237] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 144, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 144, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0238] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 144, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 144, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0239] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 145, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 145, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0240] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 145, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 145, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0241] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 146, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 146, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0242] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 146, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 146, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0243] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 147, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 147, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0244] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 147, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 147, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0245] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 148, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 148, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0246] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 148, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 148, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0247] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 149, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 149, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0248] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 149, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 149, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0249] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 150, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 150, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0250] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 150, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 150, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0251] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 151, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 151, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0252] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 151, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 151, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0253] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 152, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 152, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0254] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 152, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 152, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0255] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 153, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 153, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0256] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 153, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 153, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0257] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 154, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 154, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0258] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 154, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 154, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0259] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 155, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 155, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0260] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 155, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 155, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0261] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 156, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 156, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0262] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 156, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 156, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0263] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 157, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 157, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0264] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 157, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 157, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0265] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 158, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 158, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0266] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 158, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 158, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0267] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 159, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 159, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0268] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 159, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 159, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0269] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 160, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 160, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0270] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 160, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 160, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0271] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 161, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 161, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0272] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 161, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 161, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0273] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 162, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 162, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0274] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 162, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 162, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0275] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 163, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 163, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0276] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 163, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 163, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0277] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 164, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 164, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0278] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 164, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 164, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0279] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 165, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 165, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0280] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 165, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 165, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0281] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 166, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 166, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0282] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 166, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 166, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0283] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 167, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 167, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0284] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 167, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 167, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0285] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 168, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 168, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0286] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 168, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 168, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0287] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 169, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 169, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0288] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 169, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 169, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0289] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 170, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 170, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0290] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 170, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 170, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0291] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 171, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 171, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0292] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 171, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 171, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0293] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 172, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 172, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0294] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 172, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 172, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0295] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 173, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 173, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0296] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 173, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 173, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0297] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 174, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 174, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0298] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 174, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 174, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0299] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 175, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 175, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0300] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 175, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 175, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0301] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 176, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 176, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0302] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 176, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 176, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0303] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 250, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 250, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0304] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 250, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 250, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0305] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 251, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 251, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0306] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 251, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 251, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0307] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 252, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 252, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0308] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 252, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 252, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0309] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 253, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 253, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0310] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 253, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 253, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0311] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 254, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 254, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0312] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 254, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 254, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0313] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 255, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 255, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0314] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 255, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 255, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0315] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 256, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 256, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0316] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 256, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 256, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0317] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 257, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 257, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0318] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 257, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 257, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0319] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 258, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 258, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0320] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 258, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 258, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0321] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 259, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 259, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0322] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 259, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 259, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0323] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 260, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 260, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0324] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 260, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 260, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0325] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 261, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 261, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0326] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 261, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 261, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0327] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 262, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 262, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0328] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 262, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 262, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0329] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 263, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 263, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0330] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 263, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 263, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0331] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 264, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 264, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0332] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 264, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 264, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0333] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 265, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 265, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0334] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 265, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 265, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0335] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 266, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 266, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0336] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 266, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 266, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0337] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 267, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 267, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0338] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 267, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 267, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0339] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 268, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 268, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0340] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 268, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 268, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0341] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 269, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 269, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0342] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 269, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 269, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0343] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 270, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 270, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0344] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 270, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 270, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0345] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 271, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 271, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0346] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 271, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 271, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0347] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 272, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 272, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0348] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 272, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 272, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0349] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 273, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 273, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0350] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 273, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 273, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0351] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 274, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 274, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0352] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 274, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 274, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0353] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 275, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 275, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0354] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 275, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 275, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0355] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 276, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 276, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0356] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 276, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 276, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0357] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 277, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 277, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0358] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 277, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 277, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0359] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 278, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 278, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0360] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 278, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 278, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0361] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 279, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 279, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0362] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 279, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 279, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0363] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 280, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 280, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0364] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 280, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 280, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0365] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 281, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 281, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0366] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 281, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 281, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0367] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 282, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 282, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0368] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 282, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 282, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0369] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 283, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 283, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0370] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 283, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 283, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0371] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 284, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 284, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0372] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 284, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 284, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0373] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 285, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 285, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0374] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 285, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 285, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0375] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 286, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 286, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0376] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 286, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 286, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0377] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 287, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 287, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0378] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 287, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 287, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0379] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 288, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 288, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0380] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 288, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 288, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0381] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 289, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 289, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0382] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 289, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 289, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0383] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 290, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 290, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0384] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 290, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 290, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0385] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 291, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 291, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0386] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 291, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain having the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 291, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0387] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 292, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 292, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0388] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 292, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 292, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0389] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 293, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 293, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0390] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 293, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 293, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0391] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 294, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 294, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0392] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 294, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8, but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 294, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0393] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 295, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 295, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0394] In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule comprises the amino acid sequence of SEQ ID NO: 295, and the second heavy chain of the FcRn / antigen-binding molecule comprises an Fc domain comprising the amino acid sequence of SEQ ID NO: 8 but does not comprise an antigen-binding domain. In some embodiments, the first heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 295, and the second heavy chain of the FcRn / antigen-binding molecule consists of the amino acid sequence of SEQ ID NO: 8.

[0395] In some embodiments, the FcRn / antigen-binding molecule comprises any one amino acid sequence or a variant thereof of SEQ ID NOs: 137-176 and 250-295 described herein, and one or more amino acids added at the C-terminus. In some embodiments, the FcRn / antigen-binding molecule comprises any one amino acid sequence or a variant thereof of SEQ ID NOs: 137-176 and 250-295 described herein, and one or more amino acids added at the C-terminus, and the one or more amino acids are selected from A, AG, GG, and PP.

[0396] Polynucleotide, Vector, and Production Method The present disclosure also provides polynucleotides encoding the FcRn / antigen-binding molecules or fragments thereof disclosed herein. In some embodiments, the polynucleotide encodes an antigen-binding domain of the present disclosure. In some embodiments, the polynucleotide encodes an FcRn-binding molecule of the present disclosure. In some embodiments, the polynucleotide encodes an Fc region of the present disclosure. In some embodiments, the polynucleotide encodes an Fc domain of the present disclosure. In some embodiments, the polynucleotide encodes one or more of an antigen-binding domain, an FcRn-binding molecule, and a linker. In some embodiments, the polynucleotide encodes an antigen-binding domain and an FcRn-binding molecule, and optionally encodes a linker. In some embodiments, the polynucleotide encodes one or more of an antigen-binding domain, an Fc region, and a linker. In some embodiments, the polynucleotide encodes an antigen-binding domain and an Fc region, and optionally encodes a linker. In some embodiments, the polynucleotide encodes an FcRn / antigen-binding molecule comprising one antigen-binding domain and an Fc region. In some embodiments, the polynucleotide encodes one or more of an antigen-binding domain, an Fc domain, and a linker. In some embodiments, the polynucleotide encodes an antigen-binding domain and an Fc domain, and optionally encodes a linker. In some embodiments, the polynucleotide encodes an FcRn / antigen-binding molecule comprising one antigen-binding domain and one or more Fc domains. In some embodiments, the polynucleotide encodes one or more heavy chains of the present disclosure.

[0397] As used herein, an "isolated" polynucleotide or nucleic acid molecule is one that is separated from other nucleic acid molecules that are present in a natural source of the nucleic acid molecule (e.g., in a mouse or human). Also, an "isolated" nucleic acid molecule, e.g., a cDNA molecule, may be substantially free of other cellular material or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized. For example, the phrase "substantially free of" means that a preparation of a polynucleotide or nucleic acid molecule has less than about 15%, 10%, 5%, 2%, 1%, 0.5%, or 0.1% (in particular, less than about 10%) of other materials, such as cellular material, culture medium, other nucleic acid molecules, chemical precursors, and / or other chemicals. In one embodiment, the nucleic acid molecule(s) encoding the polypeptides described herein are isolated or purified.

[0398] In one aspect, polynucleotides are provided herein that comprise a nucleotide sequence encoding an FcRn binding molecule or an FcRn / antigen binding molecule described herein. In another aspect, polynucleotides are provided herein that comprise a nucleotide sequence encoding an antigen binding domain described herein. In another aspect, polynucleotides are provided herein that comprise a nucleotide sequence encoding an FcRn / antigen binding molecule described herein. In another aspect, polynucleotides are provided herein that comprise a nucleotide sequence encoding an FcRn / HSA binding molecule described herein.

[0399] A polynucleotide can comprise a nucleotide sequence encoding an sdAb (e.g., a VHH fragment), a Fab fragment, a scFv, a VH, or a VL that includes the FRs and CDRs of the antigen-binding domains described herein. The polynucleotide can also comprise a nucleotide sequence encoding an antibody mimetic described herein. In some embodiments, the polynucleotide can comprise a nucleotide sequence encoding a VHH fragment that includes the FRs and CDRs of the antigen-binding domains described herein. In some embodiments, the polynucleotide can comprise a nucleotide sequence encoding a light chain that includes the VL FRs and CDRs of the antigen-binding domains described herein, or a nucleotide sequence encoding a heavy chain that includes the VH FRs and CDRs of the antigen-binding domains and / or the Fc domains described herein. In one embodiment, the polynucleotide encodes a VH, a VL, a heavy chain, and / or a light chain of the antigen-binding domains described herein. In one embodiment, the polynucleotide encodes a first VH and a first VL of the antigen-binding domains described herein. In one embodiment, the polynucleotide encodes a second VH and a second VL of the antigen-binding domains described herein. In one embodiment, the polynucleotide encodes a first heavy chain and a first light chain of the antigen-binding domains described herein. In one embodiment, the polynucleotide encodes a second heavy chain and a second light chain of the antigen-binding domains described herein. In one embodiment, the polynucleotide encodes a VH and / or a VL, or a heavy chain and / or a light chain of the antigen-binding domains described herein.

[0400] In some embodiments, the polynucleotide can comprise a nucleotide sequence encoding the first heavy chain described herein. In some embodiments, the first heavy chain comprises an Fc domain and an antigen-binding domain linked by a linker. In some embodiments, the polynucleotide can comprise a nucleotide sequence encoding the second heavy chain described herein. In some embodiments, the second heavy chain comprises an Fc domain and an antigen-binding domain linked by a linker. In some embodiments, the first and second heavy chains are the same. In some embodiments, the first and second heavy chains are different.

[0401] In some embodiments, the first and second heavy chains have the same Fc domain. In some embodiments, the first and second heavy chains have different Fc domains. In some embodiments, the second heavy chain comprises an Fc domain but does not comprise an antigen-binding domain, and the first heavy chain comprises an Fc domain and an antigen-binding domain. In some embodiments, the second heavy chain comprises an Fc domain but does not comprise an antigen-binding domain or a linker, and the first heavy chain comprises an Fc domain and an antigen-binding domain. In some embodiments, the second heavy chain comprises an Fc domain but does not comprise an antigen-binding domain or a linker, and the first heavy chain comprises an Fc domain, an antigen-binding domain, and a linker.

[0402] In some embodiments, the polynucleotide comprises a nucleotide sequence encoding an Fc domain comprising an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 1-9. In some embodiments, the polynucleotide consists of a nucleotide sequence encoding an Fc domain comprising an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 1-9.

[0403] In some embodiments, the polynucleotide comprises a nucleotide sequence encoding an Fc domain comprising any one of the amino acid sequences of SEQ ID NOs: 1-9. In some embodiments, the polynucleotide comprises a nucleotide sequence encoding an Fc domain consisting of any one of the amino acid sequences of SEQ ID NOs: 1-9.

[0404] In some embodiments, the polynucleotide comprises a nucleotide sequence encoding two or more Fc domains. In some embodiments, the polynucleotide comprises a nucleotide sequence encoding two Fc domains. In some embodiments, the polynucleotide comprises a first nucleotide sequence encoding a first Fc domain and a second nucleotide sequence encoding a second Fc domain. In some embodiments, the first nucleotide sequence and the second nucleotide sequence are contained within different nucleic acid molecules. In some embodiments, the first nucleotide sequence and the second nucleotide sequence are contained within the same nucleic acid molecule.

[0405] In some embodiments, the first and second nucleotide sequences encode the same Fc domain. In some embodiments, both the first and second nucleotide sequences encode an Fc domain comprising an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 1-3. In some embodiments, both the first and second nucleotide sequences encode an Fc domain consisting of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 1-3. In some embodiments, both the first and second nucleotide sequences encode an Fc domain comprising any one of the amino acid sequences of SEQ ID NOs: 1-3. In some embodiments, both the first and second nucleotide sequences encode an Fc domain consisting of any one of the amino acid sequences of SEQ ID NOs: 1-3.

[0406] In some embodiments, the first and second nucleotide sequences encode different Fc domains. In some embodiments, the first nucleotide sequence encodes an Fc domain comprising an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 4-6, and the second nucleotide sequence encodes an Fc domain comprising an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 7-9. In some embodiments, the first nucleotide sequence encodes an Fc domain consisting of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 4-6, and the second nucleotide sequence encodes an Fc domain consisting of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 7-9. In some embodiments, the first nucleotide sequence encodes an Fc domain comprising any one of the amino acid sequences of SEQ ID NOs: 4-6, and the second nucleotide sequence encodes an Fc domain comprising any one of the amino acid sequences of SEQ ID NOs: 7-9. In some embodiments, the first nucleotide sequence encodes an Fc domain consisting of any one of the amino acid sequences of SEQ ID NOs: 4-6, and the second nucleotide sequence encodes an Fc domain consisting of any one of the amino acid sequences of SEQ ID NOs: 7-9. In some embodiments, when the first nucleotide sequence encodes the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the second nucleotide sequence encodes SEQ ID NO: 7 or a variant thereof. In some embodiments, when the first nucleotide sequence encodes the amino acid sequence of SEQ ID NO: 5 or a variant thereof, the second nucleotide sequence encodes SEQ ID NO: 8 or a variant thereof.In some embodiments, when the first nucleotide sequence encodes the amino acid sequence of SEQ ID NO: 6 or a variant thereof, the second nucleotide sequence encodes SEQ ID NO: 9 or a variant thereof.

[0407] In some embodiments, the first nucleotide sequence encodes an Fc domain and an antigen-binding domain, and the second nucleotide sequence encodes an Fc domain but does not encode an antigen-binding domain. The antigen-binding domain encoded by the first and / or second nucleotide sequence can be any of those described herein.

[0408] In some embodiments, the first and second nucleotide sequences also encode a peptide linker. In some embodiments, the first and second nucleotide sequences encode the same peptide linker. In some embodiments, the first and second nucleotide sequences encode different peptide linkers. In some embodiments, the first nucleotide sequence encodes an Fc domain, a peptide linker, and an antigen-binding domain, and the second nucleotide sequence encodes an Fc domain but does not encode a peptide linker or an antigen-binding domain. In some embodiments, the first nucleotide sequence encodes an antigen-binding domain, a peptide linker, and an Fc domain, and the second nucleotide sequence encodes an Fc domain but does not encode a peptide linker or an antigen-binding domain. The peptide linker encoded by the first and / or second nucleotide sequence can be any of those described herein. In some embodiments, the linker comprises the amino acid sequence of SEQ ID NO: 136, 180, or 181.

[0409] In some embodiments, the polynucleotide comprises, or consists of, a nucleotide sequence encoding a protein that comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 109, 110, 137-176, and 250-295.

[0410] In some embodiments, the polynucleotide comprises, or consists of, a nucleotide sequence encoding a protein comprising any one of the amino acid sequences of SEQ ID NOs: 109, 110, 137-176, and 250-295.

[0411] In some embodiments, the first nucleotide sequence encodes a protein comprising, or consisting of, an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 109, 110, 137-176, and 250-295, and the second nucleotide sequence encodes an Fc domain but does not encode an antigen-binding domain. Optionally, the second nucleotide sequence encodes a protein comprising an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 8.

[0412] In some embodiments, the first nucleotide sequence encodes a protein comprising any one of the amino acid sequences of SEQ ID NOs: 109, 110, 137-176, and 250-295, and the second nucleotide sequence encodes an Fc domain but does not encode an antigen-binding domain. Optionally, the second nucleotide sequence encodes a protein comprising the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first nucleotide sequence comprises a nucleotide sequence encoding a protein consisting of any one of the amino acid sequences of SEQ ID NOs: 109, 110, 137-176, and 250-295, and the second nucleotide sequence encodes an Fc domain but does not encode an antigen-binding domain. Optionally, the second nucleotide sequence encodes a protein consisting of the amino acid sequence of SEQ ID NO: 8.

[0413] In some embodiments, a third nucleotide sequence encoding a light chain is provided. In some embodiments, the third nucleotide sequence encodes a protein comprising, or consisting of, an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 107. In some embodiments, the third nucleotide sequence encodes a protein comprising, or consisting of, the amino acid sequence of SEQ ID NO: 107.

[0414] Also provided herein are polynucleotides encoding the polypeptides provided above, which are optimized, for example, by codon / RNA optimization, replacement with heterologous signal sequences, and elimination of mRNA instability elements. Thus, methods for generating optimized nucleic acids for recombinant expression by introduction of codon changes and / or elimination of inhibitory regions in mRNA can be carried out, for example, by adapting the optimization methods described in U.S. Patent Nos. 5,965,726, 6,174,666, 6,291,664, 6,414,132, and 6,794,498, all of which are hereby incorporated by reference in their entirety. For example, potential splice sites and instability elements (e.g., A / T or A / U rich elements) within the RNA can be mutated without changing the amino acids encoded by the nucleic acid sequence to increase the stability of the RNA for recombinant expression. The changes use the degeneracy of the genetic code and, for example, alternative codons for the same amino acid are used. In one embodiment, it may be desirable to change one or more codons to encode conservative mutations, e.g., similar amino acids having a similar chemical structure and properties and / or function as the original amino acid.

[0415] A polynucleotide can be obtained by any method known in the art, and the nucleotide sequence of the polynucleotide can be determined by any method known in the art. The nucleotide sequences encoding the proteins described herein, and modified versions of these antibodies, can be determined using methods well known in the art, i.e., nucleotide codons known to encode specific amino acids are assembled to generate a nucleic acid encoding the protein. Such polynucleotides encoding proteins can be assembled from chemically synthesized oligonucleotides (e.g., as described in Kutmeier G et al., (1994) BioTechniques 17:242-6, which is hereby incorporated by reference in its entirety), briefly, this involves the synthesis of overlapping oligonucleotides containing portions of the sequence encoding the antibody, annealing and ligation of these oligonucleotides, and then amplification of the ligated oligonucleotides by PCR.

[0416] Alternatively, the polynucleotides encoding the proteins described herein can be generated from nucleic acids from a suitable source (e.g., a hybridoma) using methods well known in the art (e.g., PCR and other molecular cloning methods). For example, PCR amplification using synthetic primers that hybridize to the 3' and 5' ends of a known sequence can be performed using genomic DNA obtained from hybridoma cells that produce the polypeptide of interest. Such PCR amplification methods can be used to obtain a nucleic acid containing the sequence encoding the polypeptide. The amplified nucleic acid can be cloned into a vector for expression and further cloning in a host cell.

[0417] Although clones containing nucleic acids encoding a specific polypeptide are not available, if the sequence of the polypeptide is known, the nucleic acid encoding the polypeptide can be obtained from a suitable source (e.g., a cDNA library generated from any tissue or cell expressing the polypeptides described herein, or a nucleic acid isolated therefrom, preferably polyA+RNA), by PCR amplification using synthetic primers capable of hybridizing to the 3' and 5' ends of the sequence, or by using an oligonucleotide probe specific for a particular gene sequence, for example, by cloning to identify a cDNA clone from a cDNA library encoding the polypeptide, and may be chemically synthesized or obtained. The amplified nucleic acid generated by PCR can then be cloned into a replicable cloning vector using any method well known in the art.

[0418] The DNA encoding the proteins described herein can be readily isolated and sequenced using conventional procedures. Hybridoma cells can function as a source of such DNA. When isolated, the DNA can be placed within an expression vector, which can then be transfected into a host cell, such as E. coli cells, monkey COS cells, Chinese hamster ovary (CHO) cells (e.g., CHO cells from the CHO GS System™ (Lonza)), or otherwise myeloma cells that do not produce the proteins described herein.

[0419] Also provided are polynucleotides that hybridize to a polynucleotide encoding a protein described herein under high stringency, intermediate, or low stringency hybridization conditions.

[0420] Hybridization conditions are described in the art and are known to those of skill in the art. For example, hybridization under stringent conditions can include hybridization to filter-bound DNA in 6x sodium chloride / sodium citrate (SSC) at about 45°C, followed by one or more washes in 0.2x SSC / 0.1% SDS at about 50 - 65°C, and hybridization under highly stringent conditions can include hybridization to filter-bound nucleic acid in 6x SSC at about 45°C, followed by one or more washes in 0.1x SSC / 0.2% SDS at about 68°C. Hybridization under other stringent hybridization conditions is known to and described by those of skill in the art, and reference is made, for example, to Ausubel FM et al., eds., (1989) Current Protocols in Molecular Biology, Vol. I, Green Publishing Associates, Inc. and John Wiley & Sons, Inc., New York, pages 6.3.1 - 6.3.6 and 2.10.3, which is hereby incorporated by reference in its entirety.

[0421] In one aspect, provided herein are cells (e.g., host cells), and related polynucleotides and expression vectors that express (e.g., recombinantly express) the proteins described herein. Also provided herein are vectors (e.g., expression vectors) for recombinant expression in a host cell, preferably a mammalian cell (e.g., a CHO cell), that contain a polynucleotide that includes a nucleotide sequence encoding a protein described herein. Also provided herein are host cells for recombinant expression of a protein described herein that contain such a vector. In one aspect, provided herein is a method for producing a protein described herein, the method including expressing a polypeptide from a host cell.

[0422] The recombinant expression of the proteins described herein generally involves the construction of an expression vector containing a polynucleotide encoding a polypeptide. When a polynucleotide encoding a polypeptide described herein is obtained, a vector for the production of the polypeptide can be produced by recombinant DNA techniques using techniques well known in the art. Accordingly, methods for preparing a protein by expressing a polynucleotide containing a polypeptide encoding a nucleotide sequence are described herein. Methods well known to those skilled in the art can be used to construct an expression vector containing a polypeptide coding sequence and appropriate transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo gene recombination. Also provided is a replicable vector comprising a nucleotide sequence encoding a polypeptide described herein, wherein the nucleotide sequence is operably linked to a promoter. Such a vector can include, for example, a nucleotide sequence encoding the first heavy chain of the present disclosure (see, e.g., International Publication Nos. 86 / 05807 and 89 / 01036, and U.S. Patent No. 5,122,464, which are hereby incorporated by reference in their entirety), and the second heavy chain of the present disclosure can be cloned into such a vector for the expression of the first heavy chain, the second heavy chain, or both the first and second heavy chains.

[0423] In one embodiment, the vector comprises a polynucleotide encoding an sdAb, Fab fragment, scFv, VHH fragment, VH, VL, heavy chain, and / or light chain of a polypeptide described herein. In another embodiment, the vector comprises a polynucleotide encoding VH and VL of a polypeptide described herein. In another embodiment, the vector comprises a polynucleotide encoding the heavy chain and light chain of a polypeptide described herein.

[0424] An expression vector can be transferred into a cell (e.g., a host cell) by conventional techniques, and the resulting cell can then be cultured by conventional techniques to produce the polypeptide or fragment thereof described herein. Accordingly, provided herein are host cells containing a polynucleotide encoding the polypeptide or fragment thereof described herein, or a heavy or light chain thereof, or a fragment thereof, or a single-chain antibody described herein, wherein the polynucleotide is operably linked to a promoter for expression of such a sequence in the host cell.

[0425] In one embodiment, the host cell comprises a polynucleotide comprising one of the first nucleotide sequences above and one of the second nucleotide sequences above. In another embodiment, the host cell comprises a first polynucleotide comprising one of the first nucleotide sequences above and a second polynucleotide comprising one of the first nucleotide sequences above. In another embodiment, the host cell comprises a first vector comprising one of the first nucleotide sequences above and one of the second nucleotide sequences above. In another embodiment, the host cell comprises a first vector comprising one of the first nucleotide sequences above and one of the second nucleotide sequences above, and a second vector comprising a second polynucleotide comprising one of the first nucleotide sequences above.

[0426] In some embodiments, the FcRn / antigen-binding molecule expressed by the first host cell associates with the FcRn / antigen-binding molecule expressed by the second host cell to form a two-arm type FcRn / antigen-binding molecule. In some embodiments, the FcRn / antigen-binding molecule expressed by the first host cell associates with the FcRn-binding molecule expressed by the second host cell to form a one-arm type FcRn / antigen-binding molecule. In some embodiments, provided herein is a population of host cells comprising such a first host cell and such a second host cell.

[0427] In some embodiments, a population of vectors is provided herein that includes a first vector comprising a polynucleotide encoding an FcRn / antigen-binding molecule and a second vector comprising a polynucleotide encoding an FcRn / antigen-binding molecule. In some embodiments, a population of vectors is provided herein that includes a first vector comprising a polynucleotide encoding an FcRn / antigen-binding molecule and a second vector comprising a polynucleotide encoding an FcRn-binding molecule. In some embodiments, a population of vectors is provided herein that includes a first vector comprising a polynucleotide encoding an FcRn / antigen-binding molecule and a polynucleotide encoding an FcRn / antigen-binding molecule. In some embodiments, a population of vectors is provided herein that includes a first vector comprising a polynucleotide encoding two FcRn / antigen-binding molecules.

[0428] A variety of host expression vector systems can be used to express the polypeptides described herein (see, e.g., U.S. Patent No. 5,807,715, which is hereby incorporated by reference in its entirety). Such host expression systems represent a medium in which the desired coding sequence can be produced and then purified, and also represent cells that can express the polypeptides described herein in situ when transformed or transfected with the appropriate nucleotide coding sequence. These include microorganisms such as bacteria (e.g., E. coli and B. subtilis), bacteria transformed with recombinant bacteriophage DNA, plasmid DNA, or cosmid DNA expression vectors containing, for example, an FcRn / antigen-binding molecule coding sequence; yeast (e.g., Saccharomyces and Pichia), yeast transformed with recombinant yeast expression vectors containing, for example, an FcRn / antigen-binding molecule coding sequence; insect cell lines, such as insect cell lines infected with recombinant virus expression vectors (e.g., baculovirus) containing an FcRn / antigen-binding molecule coding sequence; plant cell lines (e.g., green algae, e.g., Chlamydomonas reinhardtii), plant cell lines infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) containing, for example, an FcRn / antigen-binding molecule coding sequence, or plant cell lines transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing, for example, an FcRn / antigen-binding molecule coding sequence; or mammalian cell lines (e.g., COS (e.g., COS1 or COS), CHO, BHK, MDCK, HEK 293, NS0, PER.C6, VERO, CRL7O3O, HsS78Bst, HeLa, NIH 3T3, HEK-293T, HepG2, SP210, R1.1, B-W, L-M, BSC1, BSC40, YB / 20, and BMT10 cells), including but not limited to mammalian cell lines carrying recombinant expression constructs containing a promoter derived from the genome of a mammalian cell (e.g., the metallothionein promoter) or a promoter derived from a mammalian virus (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter).In one embodiment, the cells for expressing the FcRn / antigen-binding molecule described herein are Chinese hamster ovary (CHO) cells, e.g., CHO cells from the CHO GS System™ (Lonza). In one embodiment, the heavy and / or light chains produced by the CHO cells may have an N-terminal glutamine or glutamate residue replaced by pyroglutamic acid. In one embodiment, the cells for expressing the polypeptides described herein are human cells, e.g., human cell lines. In one embodiment, the mammalian expression vector is pOptiVEC™ or pcDNA3.3. In one embodiment, bacterial cells, e.g., Escherichia coli, or eukaryotic cells (e.g., mammalian cells) are used for the expression of recombinant polypeptides. For example, mammalian cells, e.g., CHO cells, are an effective expression system for antibodies together with a vector, e.g., the major immediate early gene promoter element from human cytomegalovirus (Foecking MK & Hofstetter H (1986) Gene 45:101-5, and Cockett MI et al., (1990) Biotechnology 8(7):662-7, each of these references is incorporated herein by reference in its entirety). In one embodiment, the polypeptides described herein are produced by CHO cells or NS0 cells. In one embodiment, the expression of the nucleotide sequence encoding the polypeptides described herein that contain 2, 3, or 4 binding sites to human FcRn is regulated by a constitutive promoter, an inducible promoter, or a tissue-specific promoter.

[0429] In the bacterial system, several expression vectors can be advantageously selected depending on the intended use for the expression of molecules. For example, when large amounts of such polypeptides are produced for the generation of pharmaceutical compositions of antibody molecules, a vector that directs the expression of a high level of fusion protein product that can be easily purified may be desirable. Such vectors include, but are not limited to, the E. coli expression vector pUR278 (Ruether U & Mueller-Hill B (1983) EMBO J 2:1791-1794), in which the coding sequence can be individually ligated into the vector in-frame with the lac Z coding region, whereby a fusion protein is produced, pUR278; and pIN vectors (Inouye S & Inouye M (1985) Nuc Acids Res 13:3101-3109, Van Heeke G & Schuster SM (1989) J Biol Chem 24:5503-5509), etc. All of these references are hereby incorporated by reference in their entirety. Also, for example, the pGEX vector can be used to express a foreign polypeptide as a fusion protein with glutathione 5-transferase (GST). Generally, such fusion proteins are soluble and can be easily purified from lysed cells by adsorption and binding to matrix glutathione agarose beads, followed by elution in the presence of free glutathione. The pGEX vector is designed to contain a thrombin or factor Xa protease cleavage site, whereby the cloned target gene product can be released from the GST moiety.

[0430] In the insect system, for example, Autographa californica nuclear polyhedrosis virus (AcNPV) can be used as a vector to express foreign genes. The virus grows in Spodoptera frugiperda cells. The coding sequences can be individually cloned into the non-essential regions of the virus (e.g., the polyhedrin gene) and placed under the control of an AcNPV promoter (e.g., the polyhedrin promoter).

[0431] In mammalian host cells, several virus-based expression systems can be used. When adenovirus is used as an expression vector, the coding sequence of interest can be ligated to an adenovirus transcription / translation control complex, such as a late promoter and a tripartite leader sequence. This chimeric gene can then be inserted into the adenovirus genome by in vitro or in vivo recombination. Insertion into a non-essential region of the viral genome (e.g., region E1 or E3) results in a recombinant virus that is viable and capable of expressing the molecule in the infected host (see, for example, Logan J & Shenk T (1984) PNAS 81(12):3655-9, which is hereby incorporated by reference in its entirety). Also, specific initiation signals may be required for efficient translation of the inserted coding sequence. These signals include the ATG initiation codon and adjacent sequences. Furthermore, the initiation codon must be in the same reading frame as the desired coding sequence to ensure translation of the entire insert. These exogenous translation control signals and initiation codons can be of various origins, both natural and synthetic. The efficiency of expression can be enhanced by including appropriate transcriptional enhancer elements, transcriptional terminators, etc. (see, for example, Bitter G et al., (1987) Methods Enzymol. 153:516-544, which is hereby incorporated by reference in its entirety).

[0432] In addition, a host cell line can be selected that modulates the expression of the inserted array or modifies and processes the gene product in a desired specific manner. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of the protein product can be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins and gene products. An appropriate cell line or host system can be selected to ensure the correct modification and processing of the foreign protein being expressed. For this purpose, eukaryotic host cells having cell machinery for the appropriate processing of primary transcripts, glycosylation, and phosphorylation of gene products can be used. Such mammalian host cells include, but are not limited to, CHO, VERO, BHK, HeLa, MDCK, HEK 293, NIH 3T3, W138, BT483, Hs578T, HTB2, BT2O, and T47D, NS0 (a mouse myeloma cell line that does not endogenously produce any immunoglobulin chains), CRL7O3O, COS (e.g., COS1 or COS), PER.C6, VERO, HsS78Bst, HEK-293T, HepG2, SP210, R1.1, B-W, L-M, BSC1, BSC40, YB / 20, BMT10, and HsS78Bst cells. In one embodiment, the proteins described herein are produced in ...

Claims

1. A heterodimeric protein comprising a variant IgG Fc region and a single antigen-binding domain linked to the variant IgG Fc region, wherein the antigen-binding domain specifically binds to a human antigen, the variant IgG Fc region comprises or consists of a first Fc domain and a second Fc domain that form a dimer, the variant Fc region comprises one or more mutations in amino acid residues that form the interface of the CH3 domain of the Fc domain, and the variant IgG Fc region comprises a knob-into-hole mutation.

2. The heterodimer protein according to claim 1, wherein the heterodimer protein has a molecular weight of about 60 to about 104 kilodaltons (kDa).

3. The heterodimer protein according to claim 1, wherein administration of a therapeutically effective amount of the heterodimer protein to a subject results in (i) a reduction in serum IgG in the subject, and / or (ii) a reduction in serum IgG in the subject by at least about 55% compared to the baseline level of serum IgG in the subject.

4. The heterodimer protein according to claim 1, wherein administration of a therapeutically effective amount of the heterodimer protein to a subject does not reduce the FcRn level and / or albumin level in the subject.

5. The heterodimer protein according to claim 1, wherein the clearance of the heterodimer protein is less than approximately 0.2, approximately 0.19, approximately 0.18, approximately 0.17, approximately 0.16, approximately 0.15, approximately 0.14, approximately 0.13, approximately 0.12, approximately 0.11, approximately 0.1, approximately 0.09, approximately 0.08, approximately 0.07, approximately 0.06, or approximately 0.05 l / hour in the subject after a single administration of a therapeutically effective amount of the heterodimer protein to the subject.

6. The terminal half-life (t) of the aforementioned heterodimeric protein １／２，ｚ ) are approximately 3, approximately 3.5, approximately 4, approximately 4.5, approximately 5, approximately 5.5, approximately 6, approximately 6.5, approximately 7, approximately 7.5, approximately 8, approximately 8.5, approximately 9, approximately 9.5, approximately 10, approximately 10.5, approximately 11, approximately 11.5, approximately 12, approximately 12.5, approximately 13, approximately 13.5, approximately 14, approximately 14.5, approximately 15, approximately 15.5, approximately 16, approximately 16.5, approximately 17, approximately 17.5, approximately 18, approximately 1 The heterodimeric protein according to claim 1, having a duration of 8.5, approximately 19, approximately 19.5, approximately 20, approximately 20.5, approximately 21, approximately 21.5, approximately 22, approximately 22.5, approximately 23, approximately 23.5, approximately 24, approximately 24.5, approximately 25, approximately 25.5, approximately 26, approximately 26.5, approximately 27, approximately 27.5, approximately 28, approximately 28.5, approximately 29, approximately 29.5, or more than approximately 30 days.

7. The heterodimeric protein according to claim 1, which binds to FcRn at pH 5.5 and / or pH 6.0 and optionally, when measured by surface plasmon resonance, binds with a higher affinity than the affinity of efgultigimod to FcRn at pH 5.5 and / or pH 6.0, or binds to FcRn at pH 5.5 and / or pH 6.0 and optionally, when measured by surface plasmon resonance, binds with a lower affinity than the affinity of efgultigimod to FcRn at pH 5.5 and / or pH 6.

0.

8. (i) The first Fc domain and / or the second Fc domain contains amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively. (ii) The first Fc domain and / or the second Fc domain contains amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively. (iii) Both the first Fc domain and the second Fc domain contain amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively. (iv) Both the first Fc domain and the second Fc domain contain amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively. (v) The first Fc domain and / or the second Fc domain contains amino acids Y, T, E, K, and Y at EU positions 252, 254, 256, 433, and 434, respectively. (vi) Both the first Fc domain and the second Fc domain contain amino acids Y, T, E, K, and Y at EU positions 252, 254, 256, 433, and 434, respectively. (vii) The first Fc domain and / or the second Fc domain contains amino acids Y, T, E, L, K, and F at EU positions 252, 254, 256, 428, 433, and 434, respectively, (viiii) Both the first Fc domain and the second Fc domain contain amino acids Y, T, E, L, K, and F at EU positions 252, 254, 256, 428, 433, and 434, respectively. The heterodimeric protein according to claim 1.

9. (i) The first Fc domain and / or the second Fc domain is an IgG1 Fc domain, (ii) The first Fc domain and / or the second Fc domain is a human IgG Fc domain, (iii) The first Fc domain and / or the second Fc domain is a human IgG1 Fc domain, (iv) Both the first Fc domain and the second Fc domain are IgG1 Fc domains. (v) Both the first Fc domain and the second Fc domain are human IgG Fc domains, (i) Both the first Fc domain and the second Fc domain are human IgG1 Fc domains, The heterodimeric protein according to claim 1.

10. (i) The antigen-binding domain is fused to the C-terminus of the first Fc domain or the second Fc domain, (ii) The N-terminus of the antigen-binding domain is fused to the C-terminus of the first Fc domain, (iii) The N-terminus of the antigen-binding domain is fused to the C-terminus of the second Fc domain, (iv) The antigen-binding domain is fused to the N-terminus of the first Fc domain or the second Fc domain, (v) The N-terminus of the first Fc domain is fused to the C-terminus of the antigen-binding domain, or (iv) The N-terminus of the second Fc domain is fused to the C-terminus of the antigen-binding domain, The heterodimeric protein according to claim 1.

11. The heterodimeric protein according to claim 10, wherein the antigen-binding domain is fused to the first Fc domain or the second Fc domain via a linker, and the linker is an inclementable linker and / or a peptide linker.

12. The heterodimeric protein according to claim 11, wherein the peptide linker is a GS linker, optionally having a length of 8 to 40 amino acids, and optionally having a length of 20 or 30 amino acids.

13. The heterodimeric protein according to claim 1, wherein the antigen-binding domain is fused to the first Fc domain or the second Fc domain via an IgG hinge region or a portion thereof.

14. The heterodimeric protein according to claim 1, wherein the first Fc domain contains amino acids E and D at EU positions 370 and 409, respectively, and the second Fc domain contains K at EU positions 357 and 399.

15. The heterodimeric protein according to claim 1, wherein the amino acid sequence of the first Fc domain further comprises amino acid W at EU position 366.

16. The heterodimeric protein according to claim 15, wherein the amino acid sequence of the first Fc domain includes or consists of an amino acid sequence selected from the amino acid sequences described in SEQ ID NO: 4, 5, or 6.

17. The heterodimeric protein according to claim 1, wherein the amino acid sequence of the second Fc domain further comprises amino acids S, A, and V at EU positions 366, 368, and 407, respectively.

18. The heterodimeric protein according to claim 17, wherein the amino acid sequence of the second Fc domain includes or consists of an amino acid sequence selected from the amino acid sequences described in SEQ ID NO: 7, 8, or 9.

19. The heterodimeric protein according to claim 1, wherein the antigen-binding domain is selected from a Fab fragment, sdAb, scFv, and an antibody mimetic.

20. The heterodimeric protein according to claim 19, wherein the sdAb is VHH.

21. The heterodimeric protein according to claim 19, wherein the antigen-binding domain specifically binds to IgE or HSA.

22. The heterodimeric protein according to claim 21, wherein the human antigen is IgE, the antigen-binding domain is a Fab fragment or scFv, and the Fab fragment or scFv comprises the HCDR1 amino acid sequence, HCDR2 amino acid sequence, and HCDR3 amino acid sequence of VH containing the amino acid sequence of SEQ ID NO: 108, and the L containing the LCDR1 amino acid sequence, LCDR2 amino acid sequence, and LCDR3 amino acid sequence of VL containing the amino acid sequence of SEQ ID NO:

107.

23. The heterodimeric protein according to claim 21, wherein the human antigen is IgE, the antigen-binding domain is a Fab fragment or scFv, the Fab fragment or scFv comprises a variable heavy chain domain (VH) and a variable light chain domain (VL), and the VH and VL comprise a CDR sequence selected from the group consisting of HCDR1 (SEQ ID NO: 101), HCDR2 (SEQ ID NO: 102), HCDR3 (SEQ ID NO: 103), LCDR1 (SEQ ID NO: 104), LCDR2 (SEQ ID NO: 105), and LCDR3 (SEQ ID NO: 106).

24. The heterodimeric protein according to claim 23, wherein VH contains or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 108, and VL contains or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:

107.

25. The heterodimeric protein according to claim 21, wherein the human antigen is HSA, the antigen-binding domain is VHH, and the VHH comprises a CDR1 amino acid sequence, a CDR2 amino acid sequence, and a CDR3 amino acid sequence of VHH, which includes an amino acid sequence selected from SEQ ID NOs: 42-74, 84-90, 120-127, and 204-249.

26. The aforementioned VHH is, a) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), b) Amino acid sequences including SEQ ID NO: 13 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), c) Amino acid sequences including SEQ ID NO: 14 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), d) Amino acid sequences including SEQ ID NO: 15 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), e) Amino acid sequences including SEQ ID NO: 16 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), f) Amino acid sequences including SEQ ID NO: 17 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), g) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 18 (CDR2), and SEQ ID NO: 12 (CDR3), h) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 19 (CDR2), and SEQ ID NO: 12 (CDR3), i) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 20 (CDR2), and SEQ ID NO: 12 (CDR3), j) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 21 (CDR2), and SEQ ID NO: 12 (CDR3), k) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 22 (CDR2), and SEQ ID NO: 12 (CDR3), l) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 23 (CDR2), and SEQ ID NO: 12 (CDR3), m) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 24 (CDR2), and SEQ ID NO: 12 (CDR3), n) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 25 (CDR2), and SEQ ID NO: 12 (CDR3), o) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 26 (CDR2), and SEQ ID NO: 12 (CDR3), p) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 27 (CDR2), and SEQ ID NO: 12 (CDR3), q) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 28 (CDR2), and SEQ ID NO: 12 (CDR3), r) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 29 (CDR2), and SEQ ID NO: 12 (CDR3), s) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 30 (CDR2), and SEQ ID NO: 12 (CDR3), t) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 31 (CDR2), and SEQ ID NO: 12 (CDR3), u) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 32 (CDR2), and SEQ ID NO: 12 (CDR3), v) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 33 (CDR2), and SEQ ID NO: 12 (CDR3), w) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 34 (CDR3), x) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 35 (CDR3), y) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 36 (CDR3), z) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 37 (CDR3), aa) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 38 (CDR3), bb) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 39 (CDR3), cc) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 40 (CDR3), dd) Amino acid sequences including SEQ ID NO: 15 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 36 (CDR3), ee) Amino acid sequences including SEQ ID NO: 15 (CDR1), SEQ ID NO: 21 (CDR2), and SEQ ID NO: 12 (CDR3), ff) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 41 (CDR2), and SEQ ID NO: 12 (CDR3), gg) Amino acid sequence including SEQ ID NO: 10 (CDR1), SEQ ID NO: 20 (CDR2), and SEQ ID NO: 36 (CDR3), hh) Amino acid sequences including SEQ ID NO: 111 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), ii) Amino acid sequences including SEQ ID NO: 112 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), jj) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 113 (CDR2), and SEQ ID NO: 12 (CDR3), kk) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 114 (CDR2), and SEQ ID NO: 12 (CDR3), ll) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 115 (CDR3), (mm) Amino acid sequence including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 116 (CDR3), nn) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 117 (CDR3), oo) Amino acid sequences including SEQ ID NO: 118 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 119 (CDR3), pp) Amino acid sequences including SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 77 (CDR3), qq) Amino acid sequences including SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 78 (CDR3), rr) Amino acid sequences including SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 79 (CDR3), ss) Amino acid sequences including SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 80 (CDR3), tt) Amino acid sequences including SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 81 (CDR3), uu) Amino acid sequences including SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 82 (CDR3), vv) Amino acid sequences including SEQ ID NO: 75 (CDR1), SEQ ID NO: 76 (CDR2), and SEQ ID NO: 83 (CDR3), ww) Amino acid sequences including SEQ ID NO: 182 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), xx) Amino acid sequence including SEQ ID NO: 14 (CDR1), SEQ ID NO: 27 (CDR2), and SEQ ID NO: 12 (CDR3), yy) Amino acid sequence including SEQ ID NO: 14 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 34 (CDR3), zz) Amino acid sequence including SEQ ID NO: 14 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 35 (CDR3), aaa) Amino acid sequence including SEQ ID NO: 14 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 37 (CDR3), bbb) Amino acid sequences including SEQ ID NO: 183 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 36 (CDR3), CCC) Amino acid sequences including SEQ ID NO: 16 (CDR1), SEQ ID NO: 27 (CDR2), and SEQ ID NO: 12 (CDR3), ddd) Amino acid sequences including SEQ ID NO: 16 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 34 (CDR3), eee) Amino acid sequence including SEQ ID NO: 16 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 35 (CDR3), fff) Amino acid sequences including SEQ ID NO: 16 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 37 (CDR3), ggg) Amino acid sequence including SEQ ID NO: 184 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 36 (CDR3), hhh) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 27 (CDR2), and SEQ ID NO: 34 (CDR3), iii) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 27 (CDR2), and SEQ ID NO: 35 (CDR3), jjj) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 27 (CDR2), and SEQ ID NO: 37 (CDR3), kkk) Amino acid sequences including SEQ ID NO: 15 (CDR1), SEQ ID NO: 27 (CDR2), and SEQ ID NO: 36 (CDR3), lll) Amino acid sequences including SEQ ID NO: 185 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), The amino acid sequence including sequence number 118 (CDR1), sequence number 11 (CDR2), and sequence number 12 (CDR3), nnn) Amino acid sequences including SEQ ID NO: 186 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 12 (CDR3), ooo) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 187 (CDR2), and SEQ ID NO: 12 (CDR3), ppp) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 188 (CDR2), and SEQ ID NO: 12 (CDR3), qqq) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 189 (CDR2), and SEQ ID NO: 12 (CDR3), rrr) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 190 (CDR2), and SEQ ID NO: 12 (CDR3), sss) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 191 (CDR2), and SEQ ID NO: 12 (CDR3), ttt) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 192 (CDR2), and SEQ ID NO: 12 (CDR3), uuu) Amino acid sequence including SEQ ID NO: 10 (CDR1), SEQ ID NO: 193 (CDR2), and SEQ ID NO: 12 (CDR3), vvv) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 194 (CDR2), and SEQ ID NO: 12 (CDR3), www) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 195 (CDR2), and SEQ ID NO: 12 (CDR3), xxx) Amino acid sequence including SEQ ID NO: 10 (CDR1), SEQ ID NO: 196 (CDR2), and SEQ ID NO: 12 (CDR3), yyy) Amino acid sequence including SEQ ID NO: 10 (CDR1), SEQ ID NO: 197 (CDR2), and SEQ ID NO: 12 (CDR3), zzz) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 198 (CDR2), and SEQ ID NO: 12 (CDR3), aaaa) Amino acid sequence including SEQ ID NO: 10 (CDR1), SEQ ID NO: 199 (CDR2), and SEQ ID NO: 12 (CDR3), bbbb) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 200 (CDR2), and SEQ ID NO: 12 (CDR3), cccc) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 201 (CDR2), and SEQ ID NO: 12 (CDR3), dddd) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 119 (CDR3), The amino acid sequence including sequence number 10 (CDR1), sequence number 11 (CDR2), and sequence number 202 (CDR3), and ffff) Amino acid sequences including SEQ ID NO: 10 (CDR1), SEQ ID NO: 11 (CDR2), and SEQ ID NO: 203 (CDR3) A heterodimeric protein according to claim 25, comprising an amino acid sequence selected from the group consisting of the following.

27. The heterodimeric protein according to claim 26, wherein the VHH comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to an amino acid sequence selected from the amino acid sequences described in SEQ ID NOs. 42-74, 84-90, 120-127, or 204-249.

28. The heterodimeric protein according to claim 27, further comprising one or more additional amino acids at the C-terminus of the VHH.

29. The one or more additional amino acids mentioned above a) A, b) AG, c) GG, and d) A heterodimeric protein according to claim 28, selected from the group consisting of PP.

30. A heterodimeric protein comprising a first heavy chain, wherein the first heavy chain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences of SEQ ID NOs: 109, 110, 137-176, or 250-295, or the heterodimeric protein comprising any one of the amino acid sequences of SEQ ID NOs: 109, 110, 137-176, or 250-295.

31. The heterodimeric protein according to claim 30, wherein the first heavy chain further comprises one or more amino acids added to the C-terminus of the first heavy chain, and the one or more amino acids are optionally selected from A, AG, GG, and PP.

32. The heterodimer protein according to claim 30, wherein the heterodimer protein further comprises a second heavy chain, the second heavy chain consisting of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 8, or the second heavy chain consists of the amino acid sequence of SEQ ID NO:

8.

33. The heterodimeric protein further comprises a light chain, the heavy chain containing or consisting of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 109, and the light chain containing or consisting of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 107, or The heterodimeric protein according to claim 30, wherein the heavy chain contains or consists of the amino acid sequence of SEQ ID NO: 109, and the light chain contains or consists of the amino acid sequence of SEQ ID NO:

107.

34. One or more isolated polynucleotides encoding a heterodimeric protein according to any one of claims 1 to 33.

35. An expression vector comprising one or more isolated polynucleotides as described in claim 34.

36. A host cell comprising one or more isolated polynucleotides as described in claim 34.

37. A method for producing a heterodimeric protein, comprising culturing the host cells described in claim 36 under conditions that enable the expression of the heterodimeric protein.

38. A pharmaceutical composition comprising a heterodimeric protein according to any one of claims 1 to 33 and at least one pharmaceutically acceptable carrier.

39. A pharmaceutical composition for use in reducing serum IgG in a subject, comprising a heterodimeric protein according to any one of claims 1 to 33.

40. A pharmaceutical composition for use in the treatment of antibody-mediated disorders in a subject, comprising a heterodimeric protein according to any one of claims 1 to 33.

41. The pharmaceutical composition according to claim 40, wherein the antibody-mediated disorder is an IgG-mediated disorder.

42. The pharmaceutical composition according to claim 40, wherein the antibody-mediated disorder is an autoimmune disease.

43. The aforementioned autoimmune diseases include allograft rejection, alopecia areata, ankylosing spondylitis, antiphospholipid syndrome, autoimmune Addison's disease, Alzheimer's disease, antineutrophil cytoplasmic autoantibodies (ANCA), autoimmune diseases of the adrenal gland, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune myocarditis, autoimmune neutropenia, autoimmune oophoritis and orchitis, immune thrombocytopenia (ITP or idiopathic thrombocytopenic purpura), and idiopathic thrombocytopenic purpura.Purpura), immune-mediated thrombocytopenia, or primary immune thrombocytopenia), autoimmune urticaria, Behçet's disease, bullous pemphigoid (BP), cardiomyopathy, Castleman syndrome, celiac plue dermatitis, chronic fatigue immune deficiency syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), Churg-Strauss syndrome, scarring pemphigoid, CREST syndrome, cold agglutination disorder, Crohn's disease, dilated cardiomyopathy, discoid lupus erythematosus, acquired epidermolysis bullosa, essential mixed cryoglobulinemia, VI Factor II deficiency, fibromyalgia-fibromyitis, glomerulonephritis, Graves' disease, Guillain-Barré, Goodpasture syndrome, graft-versus-host disease (GVHD), Hashimoto's thyroiditis, hemophilia A, idiopathic inflammatory myopathy (IIM), idiopathic membranous nephropathy, idiopathic pulmonary fibrosis, IgA nephropathy, IgM polyneuropathy, immune-mediated necrotizing myopathy (IMNM), juvenile arthritis, Kawasaki disease, lichen planus, lichen sclerosing, lupus erythematosus, lupus nephritis, Meniere's disease, mixed connective tissue disease, mucosal pemphigoid, multiple sclerosis, type 1 diabetes, Multifocal motor neuropathy (MMN), myasthenia gravis (MG), generalized myasthenia gravis (gMG), myositis, paraneoplastic bullous pemphigoid, bullous pemphigoid of pregnancy, pemphigus vulgaris (PV), pemphigus foliaceus (PF), pernicious anemia, polyarteritis nodosa, polychondritis, polyglandular syndrome, polymyalgia rheumatica, polymyositis, dermatomyositis (DM), necrotizing autoimmune myopathy (NAM), anti-synthetase syndrome (ASyS), primary agammaglobulinemia, primary biliary cirrhosis, psoriasis, psoriatic arthritis, relapsing polychondritis, ray A pharmaceutical composition according to claim 42, selected from the group consisting of No's phenomenon, Reiter's syndrome, rheumatoid arthritis, sarcoidosis, scleroderma, Sjögren's syndrome, parenchymal organ transplant rejection, Stiffman syndrome, systemic lupus erythematosus, Takayasu's arteritis, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), temporal arteritis / giant cell arteritis, thrombotic thrombocytopenic purpura, ulcerative colitis, uveitis, herpetiform dermatitis vasculitis, anti-neutrophil cytoplasmic antibody-associated vasculitis, vitiligo, and Wegener's granulomatosis.

44. The pharmaceutical composition according to claim 40, wherein the heterodimeric protein or antigen-binding domain is administered to the target simultaneously with or sequentially with an additional therapeutic agent.

Images