CN116234827A - Antibodies specifically recognizing FcRn and uses thereof - Google Patents

Antibodies specifically recognizing FcRn and uses thereof Download PDF

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CN116234827A
CN116234827A CN202280003350.6A CN202280003350A CN116234827A CN 116234827 A CN116234827 A CN 116234827A CN 202280003350 A CN202280003350 A CN 202280003350A CN 116234827 A CN116234827 A CN 116234827A
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张磊
张帅
晏丽
于茂荣
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Staidson Beijing Biopharmaceutical Co Ltd
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Abstract

Antibodies or antigen binding fragments that specifically recognize neonatal Fc receptor (FcRn), methods of making and uses thereof are provided.

Description

Antibodies specifically recognizing FcRn and uses thereof
The contents of the electronic sequence listing are incorporated herein by reference in their entirety: (text name: fcRn-seq. Xml, date of record: 2022.08.31, size: 88 KB).
Technical Field
The present invention relates to antibodies that specifically recognize neonatal Fc receptor (FcRn), methods of making and uses thereof, including methods of treating autoimmune and/or inflammatory diseases therewith.
Background
Neonatal Fc receptor (FcRn) is a receptor associated with the Major Histocompatibility Complex (MHC) class I. As a non-covalent heterodimer consisting of the alpha chain (FCGRT) and beta 2-microglobulin (B2M) (Raghavan et al 1993,Biochemistry 32:8654-8660; huber et al 1993J. Mol. Biol. 230:1077-1083), fcRn interacts with antibodies of the IgG class and binds to the constant or Fc region of IgG. FcRn was originally found in the gut of neonatal rats. The neonatal rats ingest IgG from the maternal milk and enter the blood of the neonate through the intestinal epithelium, thus conferring passive humoral immunity to the neonate (Brambell FW. The transmission of immunity from mother to young and the catabolism of immunoglobulins. Lancet.1966;2:1087-93;Simister NE,et al.Isolation and characterization of an Fc receptor from neonatal rat small intestine.Eur J Immunol.1985;15:733-8). Later studies found a similar functional pattern in human placenta, with FcRn transferring maternal IgG to the fetus via syncytia (Leach JL, et al isolation from human placenta of the IgG transporter, fcRn, and localization to the syncytiotrophoblast: implications for maternal-total anti-ibody transport. J immunol.1996; 157:3317-22).
FcRn plays an important role in regulating the dynamic behavior of IgG antibodies in vivo, including distribution, transport, and persistence. The determination of these activities far exceeds the role of FcRn, which was originally acting as a transporter for IgG from parent to young, facilitating a broad analysis of FcRn's molecular and cellular properties. FcRn is widely expressed in parenchymal cells (endothelial cells, epithelial cells) and hematopoietic cells (Zhu, X.et al (2001) MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dental cells J.Immunol.166,3266-3276;Akilesh,S.et al (2007) Neonatal FcR expression in bone marrow-derived cells functions to protect serum IgG from catabolism.J.Immunol.179,4580-4588; perez-Montoyo, H.et al (2009) Conditional deletion of the MHC Class I-related receptor, fcRn, reveals the sites of IgG homeostasis in mic Proc. Natl. Acad. Sci.U.S. A.106, 2788-2793). FcRn resides primarily in early acidic endosomes, binding to the Fc region of IgG in a pH-dependent manner: has an affinity of micromolar to nanomolar at pH6.5, whereas FcRn has a low binding affinity to Fc at physiological pH conditions, which is negligible. FcRn regulates serum IgG concentration by: bind and protect endocytic monomeric IgG from degradation in lysosomal compartments and transport IgG to the cell surface for release under neutral extracellular physiological pH conditions. By this mechanism, fcRn extends the half-life of IgG in serum; while IgG that is not bound by FcRn enters the lysosomal pathway and is degraded (Raghavan, m.et al. (1995) Analysis of the pH dependence of the neonatal Fc receptor/immunoglobulin G interaction using antibody and receptor derivatives. Biochemistry 34,14649-14657;Zhou,J.et al. (2003) Generation of mutated variants of the human form of the MHC class I-related receptor, fcRn, with increased affinity for mouse immunoglobulin g.j.mol.biol.332, 901-913).
FcRn binds not only the Fc region of IgG, but also serum albumin (HSA). As with IgG binding, fcRn binding to HSA is also pH dependent, with binding at acidic pH (typically less than pH6, optimally pH 5), but not at neutral pH. FcRn binding to serum albumin also protects HSA from degradation, thereby extending serum albumin half-life.
FcRn plays an important role in regulating IgG levels, making FcRn inhibitors a target for lowering antibody levels that cause symptoms, such as in autoimmune or inflammatory diseases. FcRn deficient mice are more resistant to autoimmune diseases caused by pathogenic IgG autoantibodies because they are unable to maintain high concentrations of pathogenic IgG (Christianson et al, 1996, J. Immunol.156:4932-4939; ghetie et al, 1996, eur. J. Immunol.26:690-696; israel et al, 1996, immunol. 89:573-578). In non-human primates, fcRn-based inhibitors have shown that they induce a significant reduction in the persistence of endogenous IgG levels in healthy volunteers and have a positive impact on the autoimmune disease amyotrophic disease (Nixon, a.e. et al (2015) Fully human monoclonal antibody inhibitors of the neonatal Fc receptor reduce circulating IgG in non-human matrices. Front. Immunol.6,176; kiessling, p.et al (2017) The FcRn inhibitor Rozanolixizumab reduces human serum IgG concentration: a randomized phase 1 student. Sci. Trans. Med.9, ean1208). Therefore, specifically blocking the interaction of FcRn with IgG can promote the degradation of pathogenic IgG antibodies, and thus can be used for the treatment of IgG-mediated autoimmune diseases, inflammatory diseases, and the like. anti-FcRn antibodies are described in patent WO2014/19727, WO 2015/71330. However, there remains a need for improved anti-FcRn antibodies.
The disclosures of all publications, patents, patent applications, and published patent applications mentioned herein are incorporated by reference in their entirety.
Summary of the application
In some embodiments, an isolated anti-FcRn antibody is provided comprising a heavy chain variable domain (V H ) The V is H Comprising: heavy chain complementarity determining region (HC-CDR) 1 comprising TYMN (SEQ ID NO: 1); HC-CDR2 comprising YIsX 1 X 2 SX 3 X 4 IYYADSVKG (SEQ ID NO: 44), wherein X 1 Is H or R, X 2 G, K, R or S, X 3 Is D or S, X 4 I, K or L; and HC-CDR3 comprising SWGX 1 X 2 GFDX 3 (SEQ ID NO: 45), wherein X 1 A, K, R or V, X 2 A, I or V, X 3 I, L or V; light chain variable domains (V L ) The V is L Comprising: light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLX 1 X 2 X 3 X 4 GX 5 Nyld (SEQ ID NO: 46), wherein X 1 G, I, L or V, X 2 G, H, Q or Y, X 3 E, S or V, X 4 Is N or S, X 5 Is F or Y; LC-CDR2 comprising LGSNRAS (SEQ ID NO: 29); and LC-CDR3 comprising X 1 QX 2 X 3 X 4 X 5 PT (SEQ ID NO: 47), wherein X 1 Is L or M, X 2 A, S or Y, X 3 H, I, L or V, X 4 D, G, H, Q, R or S, X 5 S, T or V.
In some embodiments, an isolated anti-FcRn antibody is provided comprising V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1 or a variant thereof comprising up to about 3 amino acid substitutions; HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9 or a variant thereof, said variant comprising up to about 3 amino acid substitutions; and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17 or a variant thereof, said variant comprising up to about 3 amino acid substitutions; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence set forth in any one of SEQ ID NOs 18-28 or a variant thereof comprising up to about 3 amino acid substitutions; LC-CDR2 comprising the amino acid sequence shown in SEQ ID No. 29 or a variant thereof comprising substitutions of up to about 3 amino acids; and LC-CDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs 30-43 or a variant thereof comprising up to about 3 amino acid substitutions.
In some embodiments, there is provided an isolated anti-FcRn antibody comprising: v (V) H The V is H Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs 48-61 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3, and V L The V is L Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs 62-82 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, there is provided an isolated anti-FcRn antibody comprising: (i) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO 48 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in the amino acid sequence SEQ ID NO. 62 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (ii) V (V) H Comprising an amino acid sequence as shown in SEQ ID NO. 49V H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 63 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (iii) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO 50 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 63 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (iv) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 64 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (v) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:52 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 65 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (vi) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:66 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (vii) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO 53 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:67 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (viii) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:54 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 68 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (ix) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:54 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:69 L Comprising LC-CDR1, LC-CDR2 andLC-CDR3；(x)V H comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in the amino acid sequence SEQ ID NO 70 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xi) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:55 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:71 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xii) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:56 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:72 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xiii) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:57 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:73 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xiv) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO 58 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 63 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xv) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:74 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xvi) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:52 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO 75 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xvii) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO 59 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Which comprisesV as shown in the amino acid sequence SEQ ID NO 76 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xviii) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:77 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xix) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:52 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:78 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xx) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:52 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:79 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xxi) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in the amino acid sequence SEQ ID NO 80 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xxii) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:60 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 81 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xxiii) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO:56 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 82 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; (xxiv) V (V) H Comprising V as shown in amino acid sequence SEQ ID NO. 61 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:66 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, a score is providedAn isolated anti-FcRn antibody comprising: (i) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:2, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:30, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (ii) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (iii) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:4, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:11, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (iv) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprisingThe amino acid sequence SEQ ID NO 10, or the V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (v) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 20, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 33, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (vi) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (vii) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising ammonia The amino acid sequences SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 35, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (viii) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:36, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (ix) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 23, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (x) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 38, or said V L Variants of (2) comprising up to about 5 amino acids in the LC-CDRsIs substituted by (a); (xi) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:13, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 39, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (xii) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:14, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 24, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (xiii) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:15, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 25, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 35, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (xiv) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO. 11, or V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (xv) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 26, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 33, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (xvi) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (xvii) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:7, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (xviii) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 41, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (xix) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 42, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (xx) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 27, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 42, or said V L Variants of (C) comprising up to about 5 amino acid substitutions in the LC-CDRs；(xxi)V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 28, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 37, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (xxii) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:16, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 43, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (xxiii) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:14, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; (xxiv) V (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO. 1, HC-CDR2 comprising the amino acid sequence SEQ ID NO. 9, and HC-CDR3 comprising the amino acid sequence SEQ IDNO:17, or V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, any of the isolated anti-FcRn antibodies described above, comprising: v (V) H Comprising an amino acid sequence set forth in any one of SEQ ID NOs 48-61 or a variant thereof having at least about 80% sequence identity to an amino acid sequence set forth in any one of SEQ ID NOs 48-61; v (V) L Comprising the amino acid sequence set forth in any one of SEQ ID NOs.62-82 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs.62-82.
In some embodiments, there is provided an isolated anti-FcRn antibody comprising: (i) V (V) H Comprising the amino acid sequence SEQ ID NO. 48 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 48; v (V) L Comprising the amino acid sequence SEQ ID NO. 62 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 62; (ii) V (V) H Comprising the amino acid sequence SEQ ID NO. 49 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 49; v (V) L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63; (iii) V (V) H Comprising the amino acid sequence SEQ ID NO. 50 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 50; v (V) L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63; (iv) V (V) H Comprising the amino acid sequence SEQ ID NO.51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 64; (v) V (V) H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 65 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 65; (vi) V (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 66; (vii) V (V) H Comprising the amino acid sequence SEQ ID NO. 53 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 53; v (V) L Comprising the amino acid sequence SEQ ID NO. 67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 67; (viii) V (V) H Comprising the amino acid sequence SEQ ID NO. 54 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 54; v (V) L Comprising the amino acid sequence SEQ ID NO. 68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 68; (ix) V (V) H Comprising the amino acid sequence SEQ ID NO. 54 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 54; v (V) L Comprising the amino acid sequence SEQ ID NO. 69 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 69; (x) V (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising an amino acid sequence70 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID No. 70; (xi) V (V) H Comprising the amino acid sequence SEQ ID NO. 55 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 55; v (V) L Comprising the amino acid sequence SEQ ID NO. 71 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 71; (xii) V (V) H Comprising the amino acid sequence SEQ ID NO. 56 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 56; v (V) L Comprising the amino acid sequence SEQ ID NO. 72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 72; (xiii) V (V) H Comprising the amino acid sequence SEQ ID NO. 57 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 57; v (V) L Comprising the amino acid sequence SEQ ID NO. 73 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 73; (xiv) V (V) H Comprising the amino acid sequence SEQ ID NO. 58 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 58; v (V) L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63; (xv) V (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 74 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 74; (xvi) V (V) H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 75 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 75; (xvii) V (V) H Comprising ammoniaA nucleotide sequence of SEQ ID NO. 59 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO. 59; v (V) L Comprising the amino acid sequence SEQ ID NO. 76 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 76; (xviii) V (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 77; (xix) V (V) H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 78; (xx) V (V) H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 79; (xxi) V (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 80 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 80; (xxii) V (V) H Comprising the amino acid sequence SEQ ID NO. 60 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 60; v (V) L Comprising the amino acid sequence SEQ ID NO. 81 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 81; (xxiii) V (V) H Comprising the amino acid sequence SEQ ID NO. 56 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 56; v (V) L Comprising the amino acid sequence SEQ ID NO. 82 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 82; (xxiv) V (V) H Comprising the amino acid sequence SEQ ID NO. 61 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 61; v (V) L Comprising the amino acid sequence SEQ ID NO. 66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 66.
In some embodiments, the isolated anti-FcRn antibody binds to human FcRn with a Kd value of 0.1pM to 1nM.
In some embodiments, an isolated anti-FcRn antibody is provided that competes with any of the above isolated anti-FcRn antibodies for specific binding to FcRn. In some embodiments, an isolated anti-FcRn antibody is provided that specifically binds to the same epitope as any of the isolated anti-FcRn antibodies described above.
In some embodiments, any of the isolated anti-FcRn antibodies described above, the isolated anti-FcRn antibody comprises an Fc fragment. In some embodiments, the isolated anti-FcRn antibody is a full length IgG antibody. In some embodiments, the isolated anti-FcRn antibody is a full length IgG1 or IgG4 antibody. In some embodiments, the isolated anti-FcRn antibody is a chimeric, fully human or humanized antibody. In some embodiments, the isolated anti-FcRn antibody is an antigen binding fragment selected from the group consisting of Fab, fab ', F (ab)' 2 Fab' -SH, single chain Fv (scFv), fv fragments, dabs, fd, nanobodies (nanobodies), diabodies (diabodies), and linear antibodies.
In some embodiments, an isolated nucleic acid molecule encoding any one of the anti-FcRn antibodies described above is provided. In some embodiments, a vector is provided, the vector comprising any one of the nucleic acid molecules described above. In some embodiments, a host cell is provided, the host cell comprising any one of the anti-FcRn antibodies described above, any one of the nucleic acid molecules described above, or any one of the vectors described above. In some embodiments, a method of making an anti-FcRn antibody is provided comprising: a) Culturing any of the above host cells under conditions effective to express an anti-FcRn antibody; and b) obtaining the expressed anti-FcRn antibody from the host cell.
In some embodiments, there is provided a method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject an effective amount of any one of the anti-FcRn antibodies described above. In some embodiments, there is provided the use of any one of the anti-FcRn antibodies described above for the preparation of a pharmaceutical composition for the treatment of a disease or disorder in a subject in need thereof. In some embodiments, there is provided the use of any one of the anti-FcRn antibodies or pharmaceutical compositions comprising an anti-FcRn antibody described above in the manufacture of a medicament for the treatment of a disease or disorder. In some embodiments, the disease or disorder is associated with FcRn signaling pathway, including autoimmune or inflammatory diseases or disorders. In some embodiments, the disease or condition is selected from, for example, myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, guillain-barre syndrome, lupus, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, rheumatoid arthritis, systemic lupus erythematosus, graves 'disease, autoimmune myocarditis, membranous glomerulonephritis, diabetes mellitus type I or type II diabetes mellitus, multiple sclerosis, raynaud's syndrome, autoimmune thyroiditis, gastritis, celiac disease, vitiligo, hepatitis, primary biliary cirrhosis, inflammatory bowel disease, spondyloarthropathies, experimental autoimmune encephalomyelitis, immune neutropenia, juvenile onset diabetes, immune responses associated with T lymphocyte mediated delayed hypersensitivity reactions common in cytokines, tuberculosis, sarcoidosis and polymyositis, polyangiitis, cutaneous vasculitis, pemphigus, pemphigoid, phosphotides, systemic sclerosis, szechuan of the like, and anti-inflammatory syndrome.
Also provided are pharmaceutical compositions, kits and articles of manufacture comprising any one of the anti-FcRn antibodies described above.
Drawings
FIGS. 1A-1B show the binding affinities of exemplary anti-FcRn antibodies to different subunits FCGRT and B2M of human hFcRn as analyzed by ELISA. FIG. 1A shows the binding affinities of exemplary anti-FcRn antibodies F02, F03, F14, F09, and F18 to human hFcRn subunit FCGRT as analyzed by ELISA. FIG. 1B shows the binding affinities of exemplary anti-FcRn antibodies F02, F03, F14, F09, and F18 to subunit B2M of human hFcRn as analyzed by ELISA.
Figures 2A-2C show the cross-reactivity of exemplary anti-FcRn antibodies analyzed by ELISA to bind FcRn of different species. Figure 2A shows the cross-reactivity of exemplary anti-FcRn antibodies F02, F03, F14, F09, and F18 binding to cynomolgus cyFcRn analyzed by ELISA. Figure 2B shows the cross-reactivity of exemplary anti-FcRn antibodies F02, F03, F14, F09, and F18 binding to rat FcRn analyzed by ELISA. Figure 2C shows the cross-reactivity of exemplary anti-FcRn antibodies F02, F03, F14, F09, and F18 binding to mouse mfcr analyzed by ELISA.
Figure 3 shows that exemplary anti-FcRn antibodies F02, F03, F14, F09, or F18 do not affect HSA content in cyno.
Fig. 4 shows that exemplary anti-FcRn antibodies F02, F03, F14, F09, F18, as well as control antibodies rozanoliximab (UCB, anti-FcRn antibody) were able to rapidly reduce IgG levels in mice.
Detailed description of the present application
In one aspect, the present application provides anti-FcRn antibody molecules. Through a combination of natural yeast library screening, affinity maturation, and appropriately designed biochemical and biological experiments, highly potent antibody molecules have been identified that are capable of binding human FcRn and inhibiting the action of human FcRn on its receptor. The results presented herein demonstrate that the antibodies in this application are even more effective or comparable to the known and widely used anti-FcRn antibodies Rozanolixizumab (UCB) as demonstrated in various biological experiments.
anti-FcRn antibodies provided herein include, for example, full length anti-FcRn antibodies, anti-FcRn single chain antibodies (scFvs), anti-FcRn Fc fusion proteins, multi-specific (e.g., bispecific) anti-FcRn antibodies, anti-FcRn immunoconjugates, and the like.
In another aspect, the present application providesAn anti-FcRn antibody, the anti-FcRn antibody comprising: heavy chain variable domain (V H ) The V is H Comprising: heavy chain complementarity determining region (HC-CDR) 1 comprising TYMN (SEQ ID NO: 1); HC-CDR2 comprising YIsX 1 X 2 SX 3 X 4 IYYADSVKG (SEQ ID NO: 44), wherein X 1 Is H or R, X 2 G, K, R or S, X 3 Is D or S, X 4 I, K or L; and HC-CDR3 comprising SWGX 1 X 2 GFDX 3 (SEQ ID NO: 45), wherein X 1 A, K, R or V, X 2 A, I or V, X 3 I, L or V; light chain variable domains (V L ) The V is L Comprising: light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLX 1 X 2 X 3 X 4 GX 5 Nyld (SEQ ID NO: 46), wherein X 1 G, I, L or V, X 2 G, H, Q or Y, X 3 E, S or V, X 4 Is N or S, X 5 Is F or Y; LC-CDR2 comprising LGSNRAS (SEQ ID NO: 29); and LC-CDR3 comprising X 1 QX 2 X 3 X 4 X 5 PT (SEQ ID NO: 47), wherein X 1 Is L or M, X 2 A, S or Y, X 3 H, I, L or V, X 4 D, G, H, Q, R or S, X 5 S, T or V.
Also provided are nucleic acids encoding anti-FcRn antibodies, compositions comprising anti-FcRn antibodies, and methods of making and using anti-FcRn antibodies.
Definition of the definition
As used herein, a "treatment" or "treatment" is a method of achieving a beneficial or desired result, including clinical results. For the purposes of this application, such beneficial or desired clinical results include, but are not limited to, one or more of the following: alleviating one or more symptoms caused by the disease, alleviating the extent of the disease, stabilizing the disease (e.g., preventing or delaying exacerbation of the disease), preventing or delaying the spread of the disease (e.g., metastasis), preventing or delaying the recurrence of the disease, delaying or slowing the progression of the disease, ameliorating the disease state, alleviating the disease (partially or wholly), reducing the dosage of one or more other drugs required to treat the disease, delaying the progression of the disease, improving or enhancing quality of life, increasing weight, and/or prolonging survival. Also, "treatment" includes reduction of disease pathology results. The methods of the present application contemplate any one or more aspects of these treatments.
The term "antibody" includes full length antibodies and antigen binding fragments thereof. Full length antibodies include two heavy chains and two light chains. The variable regions of the light and heavy chains are responsible for antigen binding. The variable region in both chains typically comprises 3 hypervariable loops, known as Complementarity Determining Regions (CDRs) (light chain (LC) CDRs comprise LC-CDR1, LC-CDR2 and LC-CDR3, and Heavy Chain (HC) CDRs comprise HC-CDR1, HC-CDR2 and HC-CDR 3). CDR boundaries of the antibodies or antigen binding fragments disclosed herein may be defined or recognized by Kabat, chothia or Al-Lazikani conventions (Al-Lazikani 1997;Chothia 1985;Chothia 1987;Chothia 1989;Kabat 1987;Kabat 1991). The 3 CDR regions of the heavy or light chain are inserted between flanking segments called Framework Regions (FRs) which are more conserved than the CDR regions and form a scaffold supporting the hypervariable loops. The constant regions of the heavy and light chains are not involved in antigen binding, but exhibit multiple effector functions. Antibodies are classified based on the amino acid sequence of their heavy chain constant regions. The five main classes or isotypes of antibodies are IgA, igD, igE, igG and IgM, which are characterized by having heavy chains of the alpha, delta, epsilon, gamma and mu types, respectively. Several major antibody classes are classified into subclasses, such as IgG1 (gamma 1 heavy chain), igG2 (gamma 2 heavy chain), igG3 (gamma 3 heavy chain), igG4 (gamma 4 heavy chain), igA1 (alpha 1 heavy chain), or IgA2 (alpha 2 heavy chain).
As used herein, the term "antigen-binding fragment" includes antibody fragments, e.g., diabodies (diabodies), fab ', F (ab') 2 Fv fragment, disulfide stabilized Fv fragment (dsFv), (dsFv) 2 Bispecific dsFv (dsFv-dsFv'), disulfide-stabilized diabody (ds diabody), single chain Fv (scFv), sA cFv dimer (bivalent diabody), a multispecific antibody consisting of an antibody fragment comprising one or more CDRs, a single domain antibody, a nanobody (nanobody), a domain antibody, a bivalent domain antibody, or any other antibody fragment capable of binding an antigen but not comprising an intact antibody structure. The antigen binding fragment is capable of binding the same antigen as the parent antibody or parent antibody fragment (e.g., parent scFv). Antigen binding fragments also include fusion proteins comprising the above antibody fragments. In some embodiments, an antigen binding fragment may include one or more CDRs from a particular human antibody grafted to a framework region from one or more different human antibodies.
As used herein, the term "epitope" refers to a specific group of atoms or amino acids on an antigen to which an antibody or antibody portion binds. If two antibodies or antibody portions exhibit competitive binding to an antigen, they may bind to the same epitope on the antigen.
As used herein, a first antibody "competes" with a second antibody for binding to an FcRn target when the first antibody inhibits the second antibody from binding to the FcRn target by at least 50% (e.g., at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%) at an equimolar concentration, and vice versa. PCT publication WO03/48731 describes a high throughput antibody "epitope categorization" method based on cross-competition.
As used herein, the term "specifically binds," "specifically recognizes," or "specific for," refers to a measurable and reproducible interaction, e.g., binding of an antibody to a target can determine the presence of the target in a heterogeneous population of molecules, including biomolecules. For example, an antibody being able to specifically recognize a target (which may be an epitope) means that the antibody binds to the target with a higher affinity, avidity, easier and/or longer lasting than other targets. In some embodiments, an antibody that specifically recognizes an antigen reacts with one or more antigenic determinants of the antigen with a binding affinity that is at least 10-fold greater than its binding affinity to other targets.
As used herein, an "isolated" anti-FcRn antibody refers to an anti-FcRn antibody that (1) is independent of naturally occurring proteins, (2) is free of other proteins of the same origin, (3) is expressed by cells of a different species, or (4) is not found in nature.
As used herein, the term "isolated nucleic acid" refers to nucleic acids of genomic, cDNA, or synthetic origin, or a combination thereof. According to its origin, the term "isolated nucleic acid" means (1) not related to all or part of the polynucleotide found in nature in "isolated nucleic acid" (2) operably linked to a polynucleotide not linked thereto in nature, or (3) not present in nature as part of a longer sequence.
As used herein, the term "CDR" or "complementarity determining region" means a discontinuous antigen binding site found within the variable domains of heavy and light chain polypeptides. J.biol.chem.252:6609-6616 (1977); kabat et al, U.S. Dept. Of Health and Human Services, "Sequences of proteins of immunological interest" (1991); chothia et al, J.mol.biol.196:901-917 (1987); al-Lazikani B.et Al, J.mol.biol.,273:927-948 (1997); macCallum et al, J.mol. Biol.262:732-745 (1996); abhinandan and Martin, mol. Immunol.,45:3832-3839 (2008); lefranc M.P.et al, dev.Comp.Immunol.,27:55-77 (2003); and honeygger and Pluckthun, J.mol.biol.,309:657-670 (2001), wherein these definitions include the coincidence or subset of amino acid residues when compared to each other. However, any definition of a CDR for an antibody or grafted antibody or variant thereof is intended to be included within the terms defined and used herein. The positions of the amino acid residues comprised by the CDRs defined by the various references cited above are listed in table 1 to illustrate the comparison. Algorithms and binding interfaces for CDR prediction are known in the art, including, for example, abhinandan and Martin, mol.immunol.,45:3832-3839 (2008); ehrenmann F.et al, nucleic Acids Res.,38:D301-D307 (2010); and Adolf-Bryfogle J.et al, nucleic Acids Res.,43:D432-D438 (2015). The contents of the references cited in this paragraph are hereby incorporated by reference in their entirety for use in this application and in one or more claims that may be included herein.
TABLE 1 CDR definition
Kabat 1 Chothia 2 MacCallum 3 IMGT 4 AHo 5
V H CDR1 31-35 26-32 30-35 27-38 25-40
V H CDR2 50-65 53-55 47-58 56-65 58-77
V H CDR3 95-102 96-101 93-101 105-117 109-137
V L CDR1 24-34 26-32 30-36 27-38 25-40
V L CDR2 50-56 50-52 46-55 56-65 58-77
V L CDR3 89-97 91-96 89-96 105-117 109-137
1 Amino acid residue numbering refers to the nomenclature used in Kabat et al, supra
2 Amino acid residue numbering refers to the nomenclature used in Chothia et al, supra
3 Amino acid residue numbering refers to the nomenclature used in MacCallum et al, supra
4 Amino acid residue numbering refers to the nomenclature used in the above-mentioned Lefranc et al
5 Amino acid residue numbering refers to the naming method in Honygger and Pluckthun, supra
The term "chimeric antibody" refers to an antibody in which a portion of the heavy and/or light chain is identical or homologous to corresponding sequences in antibodies from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical or homologous to corresponding sequences in antibodies from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they possess the biological activity herein (see U.S. patent No.4,816,567; and Morrison et al, proc.Natl. Acad. Sci. USA,81:6851-6855 (1984)).
"Fv" is the smallest antibody fragment that contains the complete antigen recognition and binding site. The fragment is a dimer formed by a tight non-covalent linkage of one heavy chain variable domain and one light chain variable domain. By folding of these two domains, 6 hypervariable loops (3 loops in each of the light and heavy chains) were derived, which Gao Bianhuan provided the amino acid residues for the antibody to bind antigen and confer specificity to the antibody for binding to antigen. However, even a single variable domain (or half of an Fv fragment, which contains only 3 CDRs specific for an antigen) has the ability to recognize and bind antigen, although with less affinity than the complete binding site.
"Single chain Fv", also abbreviated "sFv" or "scFv", is a polypeptide comprising V linked as a single polypeptide chain H And V L Antibody fragments of the antibody domains. In some embodiments, the scFv polypeptide further comprises V H And V L A linker polypeptide between the domains, which allows the scFv to form the desired structure for antigen binding. For a summary of scFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol.113, rosenburg and Moore eds., springer-Verlag, new York, pp.269-315 (1994).
The term "diabody" is in V H And V L A small antibody fragment prepared from scFv fragments (see above) is constructed using short linkers (e.g., 5-10 residues) between the domains, which allows the variable domains to pair between the chains rather than within the chains, resulting in a bivalent fragment, i.e., a fragment having two antigen binding sites. Bispecific diabodies are heterodimers of two "cross" scFv fragments, wherein V of both antibodies H And V L Domains are located on different polypeptide chains. In EP 404,097; WO 93/11161; diabodies are described fully in Hollinger et al, proc.Natl.Acad.Sci.USA,90:6444-6448 (1993).
The "humanized" form of a non-human (e.g., rodent) antibody is a chimeric antibody that includes minimal sequences from the non-human antibody. In most cases, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a hypervariable region (HVR) of the recipient antibody are replaced by residues from a hypervariable region of a non-human species, such as mouse, rat, rabbit or non-human mammal, having the desired antibody specificity, affinity and properties (donor antibody). In some cases, residues in the framework region of the human immunoglobulin are replaced with corresponding non-human residues. In addition, humanized antibodies may include residues that are not present in either the recipient antibody or the donor antibody. These modifications can further improve the performance of the antibody. Typically, a humanized antibody will comprise substantially all, at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are human immunoglobulin sequences. The human antibody optionally also includes at least a portion of an immunoglobulin constant region (Fc), typically a constant region of a human immunoglobulin. For specific details, reference may be made to Jones et al, nature 321:522-525 (1986); riechmann et al, nature 332:323-329 (1988); and Presta, curr.Op.struct.biol.2:593-596 (1992).
The "percent (%) amino acid sequence identity" or "homology" of the polypeptide and antibody sequences identified herein is defined as: sequence comparison is performed where conservative substitutions are considered to be part of the sequence identity, the percentage of amino acid residues in the candidate sequence that are identical to the polypeptide sequence to be compared. The percentage of amino acid sequence identity may be determined by a variety of alignment methods within the skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, megalign (DNASTAR), or MUSCLE software. One skilled in the art can determine suitable parameters for measuring the alignment, including any algorithms needed to achieve maximum alignment over the full length of the compared sequences. However, for purposes herein, the percent amino acid sequence identity values were generated using the sequence alignment computer program MUSCLE (Edgar, R.C., nucleic Acids Research (5): 1792-1797,2004; edgar, R.C., BMC Bioinformatics (1): 113,2004).
The term "Fc receptor" or "FcR" is used to describe a receptor that binds to the Fc region of an antibody. In some embodiments, an FcR described herein is one that binds an IgG antibody (a gamma receptor), including receptors of fcyri, fcyrii, and fcyriii subclasses, including allelic variants and alternatively spliced forms of these receptors. Fcyrii receptors include fcyriia ("activating receptor") and fcyriib ("inhibiting receptor"), which have similar amino acid sequences, differing primarily in the cytoplasmic domain. The cytoplasmic domain of the activating receptor fcyriia contains an immune receptor tyrosine activation motif (ITAM). The cytoplasmic domain of the inhibition receptor fcyriib contains the Immunoreceptor Tyrosine Inhibitory Motif (ITIM) (see m.in
Figure PCTCN2022116837-APPB-000001
Annu.Rev.Immunol.15:203-234 (1997)). The term also includes allotypes, such as fcyriiia allotypes: fcgammaRIIIA-Phe 158, fcgammaRIIIA-Val 158, fcgammaRIIA-R131 and/or FcgammaRIIA-H131. At Ravetch and Kinet, annu.Rev.Immunol 9:457-92 (1991) and Capel et al, immunomets 4:25-34 (1994); fcRs are described in de Haas et al, J.Lab.Clin.Med.126:330-41 (1995). The term FcR in this application encompasses other types of FcRs, including FcRs identified in the future. The term FcR also includes the neonatal receptor FcRn, which is responsible for transferring the parent IgGs to the neonate (Guyer et al, J.Immunol.117:587 (1976) and Kim et al, J.Immunol.24:249 (1994)).
The term "FcRn" refers to neonatal Fc receptor (FcRn). FcRn is structurally similar to the Major Histocompatibility Complex (MHC), consisting of non-covalent binding of the alpha chain to beta 2 microglobulin. The various functions of the neonatal Fc receptor FcRn are reviewed in Ghetie and Ward (2000) Annu. Rev. Immunol.18,739-766. FcRn plays an important role in the passive transport of immunoglobulin IgGs from the mother to neonates and in the regulation of serum IgG levels. FcRn acts as a salvage receptor that can bind and transport endocytosed IgG in intact form within and between cells and protect them from the default degradation pathway.
The "CH1 domain" of the human IgG heavy chain constant region typically extends from amino acid 118 to amino acid 215 (EU numbering system).
The "hinge region" is generally defined as extending from Glu at position 216 to Pro at position 230 of human IgG1 (Burton, molecular immunol.22:161-206 (1985)). The hinge regions of other IgG isotypes can be aligned with the IgG1 sequence by placing the first and last cysteine residues that form the inter-heavy chain disulfide bond in the same position as IgG 1.
The "CH2 domain" of the human IgG Fc region typically extends from amino acid 231 to amino acid 340. The CH2 domain is unique in that it does not mate tightly with another region, but rather inserts two N-terminally linked branched carbohydrate chains between the two CH2 domains of the intact native IgG molecule. It is speculated that carbohydrates may serve as a surrogate for domain-to-domain pairing, helping to keep the CH2 domain stable. Burton, molecular. Immunol.22:161-206 (1985).
The "CH3" domain includes the extension from the C-terminal residue to the CH2 domain (from amino acid 341 to the C-terminal end of the antibody sequence, typically amino acid 446 or 447 of IgG) within the Fc region.
The "functional Fc fragment" has the "effector function" possessed by the native Fc region sequence. Exemplary "effector functions" include C1q binding; complement Dependent Cytotoxicity (CDC); fc receptor binding; antibody dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down-regulation of cell surface receptors (e.g., B cell receptors; BCR), and the like. Such effector functions typically require that the Fc region bind to a binding domain (e.g., an antibody variable region) and can be assessed using a variety of experimental methods well known in the art.
Antibodies to IgG Fc variants having "altered" FcR binding affinity or ADCC activity have increased or decreased FcR binding activity and/or ADCC activity compared to the parent polypeptide or polypeptide comprising the native Fc sequence. Fc variants exhibiting "enhanced binding" to FcR have a higher binding affinity (e.g., lower apparent Kd or IC) to at least one FcR than the parent polypeptide or polypeptide comprising the native IgG Fc sequence 50 Values). In some embodiments, the binding capacity is increased by a factor of 3, e.g., 5, 10, 25, 50, 60, 100, 150, 200, even up to a factor of 500 or the binding capacity is increased by a factor of 25% to 1000% as compared to the parent polypeptide. Fc variants exhibiting "reduced binding" to FcR, which have lower affinity (e.g., higher apparent Kd or IC) for at least one FcR than the parent polypeptide 50 Values). Its binding capacity is reduced by 40% or more compared to the parent polypeptide.
"antibody-dependent cell-mediated cytotoxicity" or "ADCC" is a form of cytotoxicity that refers to the binding of secreted Ig to Fc receptors (FcRs) present on certain cytotoxic cells, such as natural killer cells (NK), neutrophils, and macrophages, enabling these cytotoxic effector cells to specifically bind antigen-bearing target cells, followed by killing of the target cells with cytotoxins. Antibodies "arm" cytotoxic cells and are necessary for such killing. In the major cell types mediating ADCC NK cells express fcyriii only, whereas monocytes express fcyri, fcyrii and fcyriii. FcR expression on hematopoietic cells is summarized in Table 3 at page 464 of Ravetch and Kinet, annu.Rev.Immunol 9:457-92 (1991). The ADCC activity of the target molecule is assessed and an in vitro ADCC assay may be performed and is described in U.S. patent nos. 5,500,362 or 5,821,337. Effector cells suitable for such experiments include Peripheral Blood Mononuclear Cells (PBMC) and natural killer cells (NK). Alternatively, or in addition, ADCC activity of the target molecule may also be assessed in vivo, for example as described in an animal model as disclosed in Clynes et al PNAS (USA) 95:652-656 (1998).
Polypeptides comprising an Fc region variant that are experimentally substantially the same in number as wild-type IgG Fc polypeptides (or parent polypeptides) are more effective in mediating ADCC in vitro or in vivo when they exhibit "enhanced ADCC activity" or are capable of mediating ADCC effects more effectively in the presence of human effector cells than wild-type IgG Fc polypeptides or parent polypeptides. Such variants are typically identified using any in vitro ADCC assay known in the art, such as assays or methods for identifying ADCC activity, e.g., in animal models, etc. In some embodiments, such variants mediate ADCC with a 5 to 100 fold, e.g., 25 to 50 fold increase in efficiency compared to the wild-type Fc (or parent polypeptide).
"complement dependent cytotoxicity" or "CDC" refers to the lysis of target cells in the presence of complement. Activation of the classical complement pathway is initiated by binding of the first component of the complement system (C1 q) to antibodies (subclasses of appropriate structure) that bind to cognate antigens. To assess complement activation, CDC experiments can be performed as described in Gazzano-Santoro et al, J.Immunol. Methods 202:163 (1996). Polypeptide variants having altered amino acid sequences of the Fc region and increased or decreased C1q binding capacity are described in U.S. Pat. No.6,194,551B1 and WO 99/51642. The contents of these patent publications are expressly incorporated herein by reference. See also Idusogie et al J.Immunol.164:4178-4184 (2000).
Unless otherwise indicated, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate versions of each other and encode the same amino acid sequence. The nucleotide sequence encoding a protein or RNA may also include introns, e.g., the nucleotide sequence encoding a protein may in some forms comprise introns.
The term "operably linked" refers to a functional linkage between a regulatory sequence and a heterologous nucleotide sequence such that the latter is expressed. For example, a first nucleotide sequence is operably linked to a second nucleotide sequence when the first nucleotide sequence is in a functional relationship with the second nucleotide sequence. For example, a promoter is operably linked to a coding sequence if it affects the transcription or expression of the coding sequence. Typically, operably linked DNA sequences are contiguous and, if necessary, two protein coding regions can be linked in the same reading frame.
"homology" refers to sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules. If the same position of two compared sequences is the same base or amino acid monomer subunit, for example, the same position of both DNA molecules is adenine, then both DNA molecules are homologous at that position. The percentage of homology between two sequences refers to the function of the ratio of the number of matching or homologous positions to the total number of positions shared by the two sequences multiplied by 100. For example, if 6 of the 10 positions in two sequences are matched or homologous, the two sequences are 60% homologous. For example, the DNA sequences ATTGCC and TATGGC have 50% homology. In general, when two sequences are aligned, alignment is performed with the aim of obtaining maximum homology.
An "effective amount" of an anti-FcRn antibody or composition disclosed herein refers to an amount sufficient to achieve a particular purpose. The "effective amount" may be determined empirically and by methods known in connection with the purpose.
The term "therapeutically effective amount" refers to an amount of an anti-FcRn antibody or composition thereof disclosed herein that is effective to treat a disease or condition in an individual. For example, in the case of autoimmune disease, a therapeutically effective amount of an anti-FcRn antibody or composition thereof refers to an amount capable of reducing the binding of IgG Fc to FcRn; reducing the half-life of circulating IgG; reducing serum IgG concentration; inhibiting (i.e., slowing or preferably stopping to some extent) the patient's autoantibody response to host tissue; suppressing (i.e., slowing or preferably stopping to some extent) the immune effector T cell response to endogenous peptides and the resulting tissue destruction. In some embodiments, the therapeutically effective amount is an FcRn blocking amount that induces overall pathogenic antibody breakdown and clearance of multiple pathogenic antibodies. In some embodiments, a therapeutically effective amount refers to an amount that is capable of extending the survival of a patient. In some embodiments, a therapeutically effective amount refers to an amount that improves the progression free survival of a patient.
As used herein, "pharmaceutically acceptable" or "pharmacologically compatible" refers to materials that are not biologically active or otherwise undesirable, e.g., that can be added to a pharmaceutical composition administered to a patient without causing significant adverse biological reactions or interacting in a deleterious manner with any of the other components of the composition in which they are contained. The pharmaceutically acceptable carrier or excipient preferably meets the desired criteria for toxicology or manufacturing testing and/or is contained in inactive ingredient guidelines established by the U.S. food and drug administration.
The embodiments of the present application described herein should be understood to include embodiments that "consist of … …" and/or "consist essentially of … …".
Reference herein to "about" is a numerical value or parameter, including (and describing) variations on the value or parameter itself. For example, a description relating to "about X" includes a description of "X".
As used herein, reference to a value or parameter that is "not (not)" generally means and describes "other than (other than)" a value or parameter. For example, the method cannot be used to treat type X cancers, meaning that the method is generally used to treat other types of cancers in addition to type X cancers.
As used herein and in the claims, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise.
anti-FcRn antibodies
In one aspect, the present application provides anti-human or/and cynomolgus FcRn antibodies that specifically bind FcRn. Such anti-FcRn antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibody molecules comprising heavy and/or light chain CDRs as described herein. In one aspect, the present application provides isolated antibodies that bind to FcRn. Contemplated anti-FcRn antibodies include, for example, full length anti-FcRn antibodies (e.g., full length IgG1 or IgG 4), anti-FcRn single chain antibodies, anti-FcRn Fc fusion proteins, multi-specific (e.g., bispecific) anti-FcRn antibodies, anti-FcRn immunoconjugates, and the like. In some embodiments, the anti-FcRn antibody is a full length antibody (e.g., full length IgG1 or IgG 4) or an antigen binding fragment thereof, which specifically binds FcRn. In some embodiments, the anti-FcRn antibody is Fab, fab ', F (ab)' 2 Fab' -SH, single chain Fv (scFv), fv fragment, dAb, fd, nanobody (nanobody), diabody (diabody), or linear antibody. In some embodiments, an antibody that specifically binds FcRn refers to an antibody that binds FcRn with at least 10-fold or more affinity than the binding affinity for the non-target (including, for example, 10 2 、10 3 、10 4 、10 5 、10 6 Or 10 7 Multiple). In some embodiments, non-target refers to an antigen that is not FcRn. Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence Activated Cell Sorting (FACS) analysis, or Radioimmunoassay (RIA). Kd values can be determined by methods known in the art, such as Surface Plasmon Resonance (SPR) techniques or Biological Layer Interferometry (BLI).
While anti-FcRn antibodies comprising human sequences (e.g., human heavy and light chain variable domains comprising human CDR sequences) are broadly discussed herein, non-human anti-FcRn antibodies are also contemplated. In some embodiments, the non-human anti-FcRn antibodies include human CDR sequences and non-human framework region sequences of the anti-FcRn antibodies described herein, and in some embodiments, the non-human framework region sequences include any sequence for producing heavy and/or light chain variable domains using one or more human CDR sequences as described herein, including, for example, mammals, e.g., mice, rats, rabbits, pigs, cattle (e.g., cattle, bulls, buffalo), deer, sheep, goats, chickens, cats, dogs, ferrets, primates (e.g., apes, macaques), and the like. In some embodiments, the non-human anti-FcRn antibody comprises an anti-FcRn antibody produced by grafting one or more of the human CDR sequences described herein into a non-human framework region (e.g., a murine or chicken framework region sequence).
An exemplary human FcRn alpha chain (FCGRT) complete amino acid sequence comprises SEQ ID NO:87 or an amino acid sequence set forth in SEQ ID NO: 87. An exemplary human FcRn chain β2-microglobulin (B2M) amino acid sequence comprises SEQ ID NO:88 or an amino acid sequence represented by SEQ ID NO:88, and a polypeptide comprising the amino acid sequence shown in seq id no.
In some embodiments, the anti-FcRn antibodies described herein specifically recognize an epitope in human FcRn. In some embodiments, the anti-FcRn antibody cross-reacts with FcRn of a species other than human. In some embodiments, the anti-FcRn antibody is fully specific for human FcRn and does not cross-react with other non-human species.
In some embodiments, the anti-FcRn antibody cross-reacts with at least one allelic variant of FcRn protein (or fragment thereof). In some embodiments, the allelic variant has up to 30 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30) amino acid substitutions (e.g., conservative substitutions) compared to the naturally occurring FcRn protein (or fragment thereof). In some embodiments, the anti-FcRn antibody does not cross-react with any allelic variant of the FcRn protein (or fragment thereof).
In some embodiments, the anti-FcRn antibody cross-reacts with at least one intervarietal variant of the FcRn protein. In some embodiments, for example, the FcRn protein (or fragment thereof) is human FcRn and the intervarietal variant of the FcRn protein (or fragment thereof) is a variant in cyno. In some embodiments, the anti-FcRn antibody does not cross-react with any inter-variant of FcRn protein.
In some embodiments, any of the anti-FcRn antibodies as described herein comprises an antibody heavy chain constant region and an antibody light chain constant region. In some embodiments, the anti-FcRn antibody comprises an IgG1 type heavy chain constant region. In some embodiments, the anti-FcRn antibody comprises an IgG2 type heavy chain constant region. In some embodiments, the anti-FcRn antibody comprises an IgG3 type heavy chain constant region. In some embodiments, the anti-FcRn antibody comprises an IgG4 type heavy chain constant region. In some embodiments, the heavy chain constant region comprises (including consisting of … or consisting essentially of …) the amino acid sequence SEQ ID NO 83. In some embodiments, the heavy chain constant region comprises (including consisting of … or consisting essentially of …) the amino acid sequence SEQ ID NO 84. In some embodiments, the anti-FcRn antibody comprises a kappa light chain constant region. In some embodiments, the light chain constant region comprises (including consisting of … or consisting essentially of …) the amino acid sequence SEQ ID NO 85. In some embodiments, the anti-FcRn antibody comprises a lambda light chain constant region. In some embodiments, the light chain constant region comprises (including consisting of … or consisting essentially of …) the amino acid sequence SEQ ID NO 86. In some embodiments, the anti-FcRn antibody comprises an antibody heavy chain variable domain and an antibody light chain variable domain.
In some embodiments, the anti-FcRn antibody comprises a heavy chain variable domain (V H ) The V is H Comprising: heavy chain complementarity determining region (HC-CDR) 1 comprising TYMN (SEQ ID NO: 1); HC-CDR2 comprising YIsX 1 X 2 SX 3 X 4 IYYADSVKG (SEQ ID NO: 44), wherein X 1 Is H or R, X 2 G, K, R or S, X 3 Is D or S, X 4 I, K or L; and HC-CDR3 comprising SWGX 1 X 2 GFDX 3 (SEQ ID NO: 45), wherein X 1 A, K, R or V, X 2 A, I of a shape of A, IOr V, X 3 I, L or V; light chain variable domains (V L ) The V is L Comprising: light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLX 1 X 2 X 3 X 4 GX 5 Nyld (SEQ ID NO: 46), wherein X 1 G, I, L or V, X 2 G, H, Q or Y, X 3 E, S or V, X 4 Is N or S, X 5 Is F or Y; LC-CDR2 comprising LGSNRAS (SEQ ID NO: 29); and LC-CDR3 comprising X 1 QX 2 X 3 X 4 X 5 PT (SEQ ID NO: 47), wherein X 1 Is L or M, X 2 A, S or Y, X 3 H, I, L or V, X 4 D, G, H, Q, R or S, X 5 S, T or V
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions; HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1, HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9, HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17.
In some embodiments, the anti-FcRn antibody comprises V L The V is L Comprising: LC-CDR1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs 18-28 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3)) Substitution of amino acids; LC-CDR2 comprising the amino acid sequence shown in SEQ ID No. 29 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30-43 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions.
In some embodiments, the anti-FcRn antibody comprises V L The V is L Comprising: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs 18-28, LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO 29, LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30-43.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions; HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs 18-28 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions; LC-CDR2 comprising the amino acid sequence shown in SEQ ID No. 29 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30-43 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1, HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9And HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs 18-28, LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30-43.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:2, HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, LC-CDR3 comprising the amino acid sequence SEQ ID NO:30, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:2, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:30.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 19, LC-CDR2, whichComprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:4, HC-CDR3 comprising the amino acid sequence SEQ ID NO:11, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:4, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:11; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising ammonia1, HC-CDR2 comprising the amino acid sequence SEQ ID NO 3, HC-CDR3 comprising the amino acid sequence SEQ ID NO 10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:20, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, LC-CDR3 comprising the amino acid sequence SEQ ID NO:33, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 20, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 33.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 35, or said V L Variants of (2) comprising up to about 5 ammonia in the LC-CDRsSubstitution of the base acid.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 35.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, LC-CDR3 comprising the amino acid sequence SEQ ID NO:36, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:36.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H Variants of (2)A substitution of up to about 5 amino acids in the HC-CDRs thereof; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 23, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 23, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 38, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence S EQ ID NO:38。
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:13, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 39, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:13; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 39.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:14, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 24, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising:HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:14; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 24, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, HC-CDR3 comprising the amino acid sequence SEQ ID NO:15, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:25, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, LC-CDR3 comprising the amino acid sequence SEQ ID NO:35, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:15; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 25, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 35.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:11, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO19, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, LC-CDR3 comprising the amino acid sequence SEQ ID NO:31, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:11; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:26, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, LC-CDR3 comprising the amino acid sequence SEQ ID NO:33, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 26, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 33.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC (HC)-CDR1 comprising the amino acid sequence SEQ ID No. 1, hc-CDR2 comprising the amino acid sequence SEQ ID No. 3, hc-CDR3 comprising the amino acid sequence SEQ ID No. 12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:7, HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:7, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 41, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 41.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 42, or said V L Variants of (C) and LC-CDRs thereofSubstitutions of up to about 5 amino acids.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 42.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 27, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO 42, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 27, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 42.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 28, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 28, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:8, HC-CDR3 comprising the amino acid sequence SEQ ID NO:16, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 43, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:16; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3Comprising the amino acid sequence SEQ ID NO. 43.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, HC-CDR3 comprising the amino acid sequence SEQ ID NO:14, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:14; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:9, HC-CDR3 comprising the amino acid sequence SEQ ID NO:17, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:9, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:17; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34.
In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs 48-61 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L The V is L Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs 62-82 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO 48 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in the amino acid sequence SEQ ID NO. 62 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO. 49 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 63 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO 50 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 63 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1. HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 64 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:52 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 65 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:66 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO 53 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:67 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:54 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 68 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:54 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:69 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising, for example, amino acid sequencesV shown in SEQ ID NO. 51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in the amino acid sequence SEQ ID NO 70 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:55 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:71 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:56 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:72 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:57 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:73 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO 58 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 63 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:74 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRnThe antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:52 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO 75 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO 59 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO 76 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:77 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:52 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:78 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:52 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:79 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in the amino acid sequence SEQ ID NO 80 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:60 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 81 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO:56 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 82 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises V H Comprising V as shown in amino acid sequence SEQ ID NO. 61 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:66 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising an amino acid sequence as set forth in any one of SEQ ID NOs 48-61 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs 48-61; v (V) L The V is L Comprising an amino acid sequence as set forth in any one of SEQ ID NOs.62-82 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs.62-82. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence shown in any one of SEQ ID NOs 48-61, and V L The V is L Comprising the amino acid sequence shown in any one of SEQ ID NOs 62-82.
In some embodiments of the present invention, in some embodiments,the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 48 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 48; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 62 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 62. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO 48 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 62.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 49 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 49; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 63. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 49 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 63.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 50 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 50; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof, said variant being identical to the amino acid sequence S EQ ID NO. 63 has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO 50 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 63.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 64 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 64. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 51 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 64.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 65 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 65. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 52 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 65.
In some embodiments, whatThe anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 66 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 66. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 51 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 66.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 53 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 53; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 67 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 67. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO 53 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 67.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 54 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 54; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 68 or a variant thereof, said variant being identical to the amino acid sequence SEQ ID NO. 68 has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 54 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 68.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 54 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 54; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 69 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 69. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 54 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 69.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 70 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 70. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 51 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 70.
In some embodiments, whatThe anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 55 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 55; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 71 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 71. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 55 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 71.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 56 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 56; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 72 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity with the amino acid sequence SEQ ID NO. 72. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 56 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 72.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 57 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity with the amino acid sequence SEQ ID NO. 57; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 73 or a variant thereof, said variant being identical to the amino acid sequence SEQ ID NO. 73 has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO 57 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 73.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 58 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 58; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 63. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO 58 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 63.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 74 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 74. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 51 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 74.
In some embodiments, whatThe anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 75 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 75. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 52 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 75.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 59 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 59; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 76 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 76. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO 59 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 76.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 77 or a variant thereof, said variant being identical to the amino acid sequence SEQ ID NO 77 has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 51 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 77.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 78 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity with the amino acid sequence SEQ ID NO. 78. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 52 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 78.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 79 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 79. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 52 and V L The V is L Comprises the amino acid sequence SEQ ID NO. 79.
In some embodiments, whatThe anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 80 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity with the amino acid sequence SEQ ID NO. 80. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 51 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 80.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 60 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 60; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 81 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 81. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 60 and V L The V is L Comprises an amino acid sequence SEQ ID NO. 81.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 56 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 56; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 82 or a variant thereof, said variant being identical to the amino acid sequence SEQID NO. 82 has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO. 56 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 82.
In some embodiments, the anti-FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 61 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 61; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 66 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence SEQ ID NO. 66. In some embodiments, the anti-FcRn antibody comprises V H The V is H Comprising the amino acid sequence SEQ ID NO 61 and V L The V is L Comprising the amino acid sequence SEQ ID NO. 66.
In some embodiments, the amino acid substitutions described above are limited to the "exemplary substitutions" shown in table 4 herein. In some embodiments, amino acid substitutions are limited to the "preferred substitutions" shown in table 4 herein.
In some embodiments, the functional epitope can be resolved by combining alanine scanning methods. In this process, combinatorial alanine scanning techniques can be used to identify amino acids in the FcRn protein that are necessary for interaction with anti-FcRn antibodies. In some embodiments, the epitope is conformational, and the crystal structure of an anti-FcRn antibody that binds to an FcRn protein may be employed to identify the epitope.
In some embodiments, the present application provides antibodies that competitively bind to FcRn with any of the anti-FcRn antibodies described herein. In some embodiments, antibodies are provided that are capable of competitively binding to an epitope on FcRn with any of the anti-FcRn antibodies described herein. In some embodimentsIn one embodiment, an anti-FcRn antibody is provided that is associated with a polypeptide comprising V H And V L Wherein said V binds to the same epitope as an anti-FcRn antibody molecule of (2) H Comprising the amino acid sequence shown in any one of SEQ ID NOs 48-61 and V L Comprising the amino acid sequence shown in any one of SEQ ID NOs 62-82. In some embodiments, an anti-FcRn antibody is provided that is associated with a polypeptide comprising V H And V L Is competitively bound to FcRn, wherein said V H Comprising the amino acid sequence shown in any one of SEQ ID NOs 48-61 and V L Comprising the amino acid sequence shown in any one of SEQ ID NOs 62-82.
In some embodiments, competition experiments may be used to identify monoclonal antibodies that competitively bind to FcRn with the anti-FcRn antibodies described herein. Competition experiments can determine whether two antibodies bind to the same epitope by recognizing the same or spatially overlapping epitopes or by one antibody competitively inhibiting the binding of the other antibody to the antigen. In certain embodiments, such a competing antibody binds to the same epitope as the antibodies described herein. Some exemplary competition experiments include, but are not limited to, routine experiments as mentioned in Harlow and Lane (1988) Antibodies A Laboratory Manual ch.14 (Cold Spring Harbor Laboratory, cold Spring Harbor, N.Y.). A detailed exemplary method for resolving epitopes bound by antibodies is described in Morris (1996), "Epitope Mapping Protocols," in Methods in Molecular Biology vol.66 (Humana Press, totowa, N.J.). In some embodiments, each antibody is said to bind to the same epitope if it blocks 50% or more of the binding of the other antibody. In some embodiments, the antibody that competes with an anti-FcRn antibody described herein is a chimeric, humanized, or fully human antibody.
Exemplary anti-FcRn antibody sequences are shown in tables 2 and 3, with CDR numbering according to the Kabat definition. Those skilled in the art will recognize that there are a variety of known algorithms to predict CDR positions and define antibody light and heavy chain variable regions. Comprising CDRs of an antibody as described herein, V H And/or V L Sequences but based on predictive algorithmsBut antibodies other than those exemplified in the tables below are also within the scope of the present application.
TABLE 2 exemplary anti-FcRn antibody CDR sequences
Figure PCTCN2022116837-APPB-000002
Figure PCTCN2022116837-APPB-000003
Figure PCTCN2022116837-APPB-000004
Table 3 exemplary sequences
Figure PCTCN2022116837-APPB-000005
Figure PCTCN2022116837-APPB-000006
Figure PCTCN2022116837-APPB-000007
Figure PCTCN2022116837-APPB-000008
FcRn
Neonatal Fc receptor (FcRn) is a receptor associated with the Major Histocompatibility Complex (MHC) class I. As a non-covalent heterodimer consisting of the alpha chain (FCGRT) and beta 2-microglobulin (B2M) (Raghavan et al 1993,Biochemistry 32:8654-8660; huber et al 1993J. Mol. Biol. 230:1077-1083), fcRn interacts with antibodies of the IgG class and binds to the constant or Fc region of IgG. FcRn was originally identified as a transporter of IgG from the mother to neonates (Leach et al, j. Immunol,157:3317, 1996), playing an important role in neonatal life, however FcRn is known today to play an important role in regulating the dynamic behavior of IgG antibodies in vivo, including distribution, transport and persistence. FcRn is widely expressed in parenchymal cells (endothelial cells, epithelial cells) and hematopoietic cells. FcRn resides primarily in early acidic endosomes, binding to the Fc region of IgG in a pH-dependent manner: has an affinity of micromolar to nanomolar at pH6.5, whereas FcRn has a weak binding affinity to Fc at physiological pH, which is negligible. FcRn regulates serum IgG concentration by: bind and protect endocytic monomeric IgG from degradation in lysosomal compartments and transport IgG to the cell surface for release under neutral extracellular physiological pH conditions. By this mechanism, fcRn extends the half-life of IgG in serum; whereas IgG not bound by FcRn enters the lysosomal pathway and is degraded. FcRn deficient mice are more resistant to autoimmune diseases caused by pathogenic IgG autoantibodies because they are unable to maintain high concentrations of pathogenic IgG (Christianson et al, 1996, J. Immunol.156:4932-4939; ghetie et al, 1996, eur. J. Immunol.26:690-696; israel et al, 1996, immunol. 89:573-578).
Full length anti-FcRn antibodies
In some embodiments, the anti-FcRn antibody is a full length anti-FcRn antibody. In some embodiments, the full length anti-FcRn antibody is IgA, igD, igE, igG or IgM. In some embodiments, the full length anti-FcRn antibody comprises an IgG constant region, e.g., a constant region of IgG1, igG2, igG3, igG4, or a variant thereof. In some embodiments, the full length anti-FcRn antibody comprises a lambda light chain constant region. In some embodiments, the full length anti-FcRn antibody comprises a kappa light chain constant region. In some embodiments, the full length anti-FcRn antibody is a full length human anti-FcRn antibody. In some embodiments, the full length anti-FcRn antibody comprises a mouse immunoglobulin Fc sequence. In some embodiments, the full length anti-FcRn antibody comprises an Fc sequence that has been altered or otherwise altered such that it has enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) effector functions.
Thus, for example, in some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided that specifically binds to FcRn. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG2 constant region is provided that specifically binds to FcRn. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG3 constant region is provided that specifically binds to FcRn. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided that specifically binds to FcRn. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions; HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and b) a light chain variable domain comprising: LC-CDR1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs 18-28 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions, LC-CDR2 comprising an amino acid sequence as set forth in SEQ ID NO 29 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30-43 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG2 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions; HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs 18-28 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions; LC-CDR2 comprising the amino acid sequence shown in SEQ ID No. 29 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30-43 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG3 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions, HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs 18-28 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions; LC-CDR2 comprising the amino acid sequence shown in SEQ ID No. 29 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30-43 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions; HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17 or a variant thereof comprising up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and b) a light chain variable domain comprising: LC-CDR1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs 18 to 28 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions, LC-CDR2 comprising an amino acid sequence as set forth in SEQ ID NO 29 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions, and LC-CDR3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs 30 to 43 or a variant thereof comprising up to about 3 (e.g. 1, 2 or 3) amino acid substitutions. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1, HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9, and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17, or a variant of said heavy chain variable domain comprising up to about 5 (e.g., 1, 2, 3, 4 or 5) amino acid substitutions in the HC-CDR sequence; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs 18 to 28, LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30 to 43, or a variant of said light chain variable domain comprising up to about 5 (e.g. 1, 2, 3, 4 or 5) amino acid substitutions in the LC-CDR sequence. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1, HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9, and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17, or a variant of said heavy chain variable domain comprising up to about 5 (e.g., 1, 2, 3, 4 or 5) amino acid substitutions in the HC-CDR sequence; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs 18 to 28, LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30 to 43, or a variant of said light chain variable domain comprising up to about 5 (e.g. 1, 2, 3, 4 or 5) amino acid substitutions in the LC-CDR sequence. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1, HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9, and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs 18-28, LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30-43. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1, HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9, and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs 18-28, LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30-43. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:2, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:30. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:4, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:11; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 20, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 33. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 35. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:36. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 23, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 38. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:13; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 39. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:14; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 24, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:15; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 25, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 35. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:11; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 26, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 33. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:7, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 41. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 42. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 27, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 42. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 28, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:16; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 43. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:14; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:9, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:17; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:2, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:30. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:4, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:11; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 20, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 33. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 35. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:36. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 23, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 38. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:13; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 39. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:14; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 24, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:15; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 25, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 35. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:11; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 26, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 33. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:7, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 41. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 42. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 27, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 42. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 28, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:16; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 43. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:14; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: a) A heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:9, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:17; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: heavy chain variable domain (V H ) The V is H Comprising an amino acid sequence as set forth in any one of SEQ ID NOs 48-61 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs 48-61; light chain variable domains (V L ) The V is L Comprising an amino acid sequence as set forth in any one of SEQ ID NOs.62-82 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs.62-82. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG2 constant region is provided, wherein the anti-FcRn antibody comprises: heavy chain variable domain (V H ) The V is H Comprising an amino acid sequence as set forth in any one of SEQ ID NOs 48-61 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99) of the amino acid sequence as set forth in any one of SEQ ID NOs 48-61% sequence identity; light chain variable domains (V L ) The V is L Comprising an amino acid sequence as set forth in any one of SEQ ID NOs.62-82 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs.62-82. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG3 constant region is provided, wherein the anti-FcRn antibody comprises: heavy chain variable domain (V H ) The V is H Comprising an amino acid sequence as set forth in any one of SEQ ID NOs 48-61 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs 48-61; light chain variable domains (V L ) The V is L Comprising an amino acid sequence as set forth in any one of SEQ ID NOs.62-82 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs.62-82. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: heavy chain variable domain (V H ) The V is H Comprising an amino acid sequence as set forth in any one of SEQ ID NOs 48-61 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs 48-61; and Light chain variable domain (V L ) The V is L Comprising an amino acid sequence as set forth in any one of SEQ ID NOs.62-82 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs.62-82. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: heavy chain variable domain (V H ) The V is H Comprising the amino acid sequence shown in any one of SEQ ID NOs 48-61 and a light chain variable domain (V L ) The V is L Comprising the amino acid sequence shown in any one of SEQ ID NOs 62-82. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a kit comprising an IgG4 constantA full length anti-FcRn antibody of the region, wherein the anti-FcRn antibody comprises: heavy chain variable domain (V H ) The V is H Comprising the amino acid sequence shown in any one of SEQ ID NOs 48-61 and a light chain variable domain (V L ) The V is L Comprising the amino acid sequence shown in any one of SEQ ID NOs 62-82. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 48 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 48; v (V) L Comprising the amino acid sequence SEQ ID NO. 62 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 62. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 49 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 49; v (V) L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 50 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 50; v (V) L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chainThe constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 64. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 65 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:85 . In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 66. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 53 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 53; v (V) L Comprising the amino acid sequence SEQ ID NO. 67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 67. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists ofThe amino acid sequence SEQ ID NO. 83 and the light chain constant region comprise or consist of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 54 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 54; v (V) L Comprising the amino acid sequence SEQ ID NO. 68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 68. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 54 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 54; v (V) L Comprising the amino acid sequence SEQ ID NO. 69 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 69. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant regionComprising or consisting of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 70 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 70. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 55 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 55; v (V) L Comprising the amino acid sequence SEQ ID NO. 71 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 71. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, lightThe chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 56 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 56; v (V) L Comprising the amino acid sequence SEQ ID NO. 72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 72. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 57 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 57; v (V) L Comprising the amino acid sequence SEQ ID NO. 73 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 73. In some embodiments, the IgG1 is human IgG1. In some embodimentsIn examples, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 58 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 58; v (V) L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 74 or a variant thereof, said variant being identical to the amino acid sequence SEQ ID NO. 74 has at least about 80% sequence identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 75 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 75. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 59 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 59; v (V) L Comprising the amino acid sequence SEQ ID NO. 76 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 76. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 77. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereofThe variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 78. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 79. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided,wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 80 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 80. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 60 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 60; v (V) L Comprising the amino acid sequence SEQ ID NO. 81 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 81. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 56 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 56; v (V) L Comprising the amino acid sequence SEQ ID NO. 82 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 82. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG1 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 61 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 61; v (V) L Comprising the amino acid sequence SEQ ID NO. 66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 66. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQID No. 83 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID No. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 48 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 48; v (V) L Comprising the amino acid sequence SEQ ID NO. 62 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 62. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 49 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 49; v (V) L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of an amino group The acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 50 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 50; v (V) L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 64. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments of the present invention, in some embodiments,the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 65 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 65. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 66. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some implementationsIn embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 53 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 53; v (V) L Comprising the amino acid sequence SEQ ID NO. 67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 67. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 54 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 54; v (V) L Comprising the amino acid sequence SEQ ID NO. 68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 68. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84.In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 54 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 54; v (V) L Comprising the amino acid sequence SEQ ID NO. 69 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 69. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 70 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 70. In some embodiments, the IgG4Is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 55 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 55; v (V) L Comprising the amino acid sequence SEQ ID NO. 71 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 71. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 56 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 56; v (V) L Comprising the amino acid sequence SEQ ID NO. 72 or a variant thereofHas at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 72. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 57 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 57; v (V) L Comprising the amino acid sequence SEQ ID NO. 73 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 73. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 58 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 58 A first property; v (V) L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 74 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 74. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising an amino acid sequenceSEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 75 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 75. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 59 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 59; v (V) L Comprising the amino acid sequence SEQ ID NO. 76 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 76. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a polypeptide comprising an IgG4 constant region is providedWherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 77. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 78. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence set SEQ ID NO:86 And (3) forming the finished product.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 79. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 80 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 80. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises orConsists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 60 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 60; v (V) L Comprising the amino acid sequence SEQ ID NO. 81 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 81. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 56 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 56; v (V) L Comprising the amino acid sequence SEQ ID NO. 82 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 82. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region The region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a full length anti-FcRn antibody comprising an IgG4 constant region is provided, wherein the anti-FcRn antibody comprises: v (V) H Comprising the amino acid sequence SEQ ID NO. 61 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 61; v (V) L Comprising the amino acid sequence SEQ ID NO. 66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 66. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
Binding affinity
Binding affinity is expressed in terms of Kd, koff, kon or Ka. As used herein, the term Koff refers to the rate constant of dissociation of an antibody from an antigen/antibody complex, as determined by a kinetic selection device. The term Kon refers to the binding rate constant of an antibody to an antigen to form an antigen/antibody complex. The equilibrium dissociation constant Kd as used herein refers to the dissociation constant at which a particular antibody antigen interacts, meaning that in a solution of an antibody molecule, the antigen occupies half of all antibody binding sites and the concentration of antigen required to reach equilibrium is equal to Koff/Kon. Determination of Kd assumes that all binding molecules are in solution. In the case of antibody attachment to the cell wall, for example in yeast expression systems, the corresponding equilibrium dissociation rate constants employ EC 50 To indicate that it is a good approximation of Kd. The affinity binding constant Ka is the inverse of the dissociation constant Kd.
The dissociation constant (Kd) can be used as an indicator of the affinity of the reactive antibody moiety for the antigen. For example, the interactions between biomolecules can be analyzed by Scatchard method using antibodies labeled with various markers, and Biacore instrument (manufactured by Amersham Biosciences) by surface plasmon resonance according to a user manual or an attached kit. The Kd values obtained using these methods are expressed in units M. Antibodies that specifically bind to the target may have, for example, 10 +. -7 M、≤10 -8 M、≤10 -9 M、≤10 -10 M、≤10 - 11 M、≤10 -12 M or less than or equal to 10 -13 Kd value of M.
The binding specificity of an antibody can be determined experimentally by methods known in the art. These methods include, but are not limited to, western blots, ELISA-, RIA-, ECL-, IRMA-, EIA-, BIAcore assays, peptide scans, and the like.
In some embodiments, the anti-FcRn antibody specifically binds to an FcRn target with a Kd value of 10 -7 M to 10 -13 M (e.g. 10 -7 M to 10 -13 M、10 -8 M to 10 -13 M、10 -9 M to 10 -13 M or 10 -10 M to 10 - 12 M). Thus, in some embodiments, the Kd value of binding between an anti-FcRn antibody and FcRn is 10 -7 M to 10 -13 M、1×10 -7 M to 5X 10 -13 M、10 -7 M to 10 -12 M、10 -7 M to 10 -11 M、10 -7 M to 10 - 10 M、10 -7 M to 10 -9 M、10 -8 M to 10 -13 M、1×10 -8 M to 5X 10 -13 M、10 -8 M to 10 -12 M、10 -8 M to 10 -11 M、10 -8 M to 10 -10 M、10 -8 M to 10 -9 M、5×10 -9 M to 1X 10 -13 M、5×10 - 9 M to 1X 10 -12 M、5×10 -9 M to 1X 10 -11 M、5×10 -9 M to 1X 10 -10 M、10 -9 M to 10 -13 M、10 -9 M to 10 -12 M、10 -9 M to 10 -11 M、10 -9 M to 10 -10 M、5×10 -10 M to 1X 10 -13 M、5×10 - 10 M to 1X 10 -12 M、5×10 -10 M to 1X 10 -11 M、10 -10 M to 10 -13 M、1×10 -10 M to 5X 10 - 13 M、1×10 -10 M to 1X 10 -12 M、1×10 -10 M to 5X 10 -12 M、1×10 -10 M to 1X 10 -11 M、10 - 11 M to 10 -13 M、1×10 -11 M to 5X 10 -13 M、10 -11 M to 10 -12 M、10 -12 M to 10 -13 M. In some embodiments, the Kd value of binding between an anti-FcRn antibody and FcRn is 10 -7 M to 10 -13 M。
In some embodiments, the Kd value of binding between an anti-FcRn antibody and a non-target is higher than the Kd value of the anti-FcRn antibody to the target, and in some embodiments cited herein, the binding affinity of the anti-FcRn antibody to the target (e.g., fcRn) is higher than the binding affinity of the anti-FcRn antibody to the non-target. In some embodiments, non-target refers to an antigen other than FcRn. In some embodiments, the anti-FcRn antibodies (directed against FcRn) have at least a 10-fold difference between Kd values for binding to the non-FcRn target, e.g., 10-100-fold, 100-1000-fold, 10-fold 3 -10 4 Multiple of 10 4 -10 5 Multiple of 10 5 -10 6 Multiple of 10 6 -10 7 Multiple of 10 7 -10 8 Multiple of 10 8 -10 9 Multiple of 10 9 -10 10 Multiple of 10 10 -10 11 Multiple of 10 11 -10 12 Multiple times.
In some embodiments, the anti-FcRn antibody binds to a non-target with a Kd value of 10 -1 M to 10 -6 M (e.g. 10 -1 M to 10 -6 M、10 -1 M to 10 -5 M、10 -2 M to 10 -4 M). In some embodiments, the non-target refers to an antigen other than FcRn. Thus, in some embodiments, the Kd value for binding between an anti-FcRn antibody and a non-FcRn target is 10 -1 M to 10 -6 M、1×10 -1 M to 5X 10 -6 M、10 -1 M to 10 -5 M、1×10 -1 M to 5X 10 -5 M、10 -1 M to 10 -4 M、1×10 -1 M to 5X 10 -4 M、10 -1 M to 10 -3 M、1×10 -1 M to 5X 10 -3 M、10 -1 M to 10 -2 M、10 -2 M to 10 -6 M、1×10 -2 M to 5X 10 -6 M、10 -2 M to 10 -5 M、1×10 -2 M to 5X 10 -5 M、10 -2 M to 10 -4 M、1×10 -2 M to 5X 10 -4 M、10 -2 M to 10 -3 M、10 -3 M to 10 -6 M、1×10 -3 M to 5X 10 -6 M、10 -3 M to 10 -5 M、1×10 -3 M to 5X 10 -5 M、10 -3 M to 10 -4 M、10 -4 M to 10 -6 M、1×10 -4 M to 5X 10 -6 M、10 -4 M to 10 -5 M、10 -5 M to 10 -6 M。
In some embodiments, when referring to an anti-FcRn antibody specifically recognizing an FcRn target with high binding affinity and binding to a non-target with low binding affinity, the anti-FcRn antibody binds to the FcRn target with a Kd value of 10 -7 M to 10 -13 M (e.g. 10 -7 M to 10 -13 M、10 -8 M to 10 -13 M、10 -9 M to 10 -13 M、10 -10 M to 10 -12 M), and Kd value of 10 for non-target binding -1 M to 10 -6 M (e.g. 10 -1 M to 10 -6 M、10 -1 M to 10 -5 M、10 -2 M to 10 -4 M)。
In some embodiments, when referring to an anti-FcRn antibody specifically recognizing FcRn, the binding affinity of the anti-FcRn antibody is compared to the binding affinity of a control anti-FcRn antibody (e.g., rozanolixizumab). In some embodiments, the Kd value for binding between a control anti-FcRn antibody and FcRn may be at least 2-fold, e.g., 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 100-fold, 1000-fold, 10-fold, the Kd value for binding between an anti-FcRn antibody and FcRn described herein 3 -10 4 Multiple times.
Nucleic acid
Nucleic acid molecules encoding anti-FcRn antibodies are also contemplated. In some embodiments, a nucleic acid (or set of nucleic acids) encoding a full-length anti-FcRn antibody is provided, including any one of the full-length anti-FcRn antibodies described herein. In some embodiments, a nucleic acid (or a set of nucleic acids) of an anti-FcRn antibody described herein may also include a nucleic acid sequence encoding a polypeptide tag (e.g., a protein purification tag, his tag, HA tag).
Also contemplated herein are isolated host cells comprising an anti-FcRn antibody, isolated nucleic acids encoding an anti-FcRn antibody polypeptide component, or vectors comprising nucleic acids encoding an anti-FcRn antibody polypeptide component described herein.
Variants of these nucleic acid sequences are also encompassed by the present application. For example, a variant comprises a nucleotide sequence that hybridizes under at least moderately stringent hybridization conditions to a nucleic acid sequence encoding an anti-FcRn antibody of the present application.
The present application also provides vectors into which the nucleic acid sequences of the present application may be inserted.
Briefly, an anti-FcRn antibody (e.g., a full length anti-FcRn antibody) may be expressed by inserting a natural or synthetic nucleic acid encoding the anti-FcRn antibody into a suitable expression vector such that the nucleic acid is operably linked to 5' and 3' regulatory elements, including, for example, promoters (e.g., lymphocyte-specific promoters) and 3' untranslated regions (UTRs). The vectors may be suitable for replication and integration in eukaryotic host cells. Typical cloning and expression vectors contain transcriptional and translational terminators, initiation sequences, and promoters that regulate the expression of a nucleic acid sequence of interest.
The nucleic acids described herein can also be used for nucleic acid immunization and gene therapy by using standard gene delivery protocols. Nucleic acid delivery methods are known in the art. See, for example, U.S. Pat. nos.5,399,346, 5,580,859, 5,589,466, the entire contents of which are incorporated herein by reference. In some embodiments, the present application also provides gene therapy vectors.
Nucleic acids can be cloned into many types of vectors. For example, the nucleic acid may be cloned into vectors including, but not limited to, plasmids, phagemids, phage derivatives, animal viruses and cosmids. Vectors of particular interest include expression vectors, replication vectors, probe-generating vectors and sequencing vectors.
In addition, the expression vector may be provided to the cell in the form of a viral vector. Viral vector technology is well known in the art and is described, for example, in Green and Sambrook (2013,Molecular Cloning:A Laboratory Manual,Cold Spring Harbor Laboratory,New York), as well as in other virology or molecular biology manuals. Viruses that may be used as vectors include, but are not limited to, retroviruses, adenoviruses, adeno-associated viruses, herpesviruses, and lentiviruses. In general, suitable vectors include an origin of replication, promoter sequences, convenient restriction enzyme sites, and one or more selectable markers that function in at least one organism (see, e.g., WO 01/96584; WO 01/29058; and U.S. Pat.No.6,326,193).
Many virus-based systems have been developed for transferring genes into mammalian cells. For example, retroviruses provide a convenient platform for gene delivery systems. The selected gene may be inserted into a vector and packaged into retroviral particles using techniques known in the art. The recombinant virus is then isolated and delivered to cells of the subject in vivo or in vitro. Many retroviral systems are known in the art. In some embodiments, an adenovirus vector is used. Many adenoviral vectors are known in the art. In some embodiments, lentiviral vectors are used. Retroviral-derived vectors, such as lentiviruses, are suitable tools for achieving long-term gene transfer, as they allow for long-term stable integration of the transgene and propagation in daughter cells. Lentiviral vectors have additional advantages over retroviruses derived from tumors, such as the mouse leukemia virus, in that they can transduce non-dividing cells, such as hepatocytes. At the same time, it has the additional advantage of low immunogenicity.
Other promoter elements, e.g., enhancers, regulate the transcription initiation frequency. Typically they are located 30-110bp upstream of the start site, although many promoters have recently been found to contain functional elements downstream of the start site as well. The spacing between promoter elements is generally flexible so that the function of the promoter is maintained when the elements are interchanged or moved in position relative to each other. In the thymidine kinase (tk) promoter, the increase in the spacing between promoter elements to 50bp activity begins to decrease.
One example of a suitable promoter is the immediate early Cytomegalovirus (CMV) promoter sequence. The promoter sequence is a strong constitutive promoter sequence capable of driving high levels of expression of any polynucleotide sequence operably linked thereto. Another example of a suitable promoter is the elongation factor 1 alpha (EF-1 alpha) promoter. However, other constitutive promoters may also be used, including but not limited to simian virus 40 (SV 40) early promoter, mouse Mammary Tumor Virus (MMTV), human immunodeficiency virus long terminal repeat (HIV-LTR) promoter, moMuLV promoter, avian leukemia virus promoter, epstein-Barr virus immediate early promoter, rous sarcoma virus promoter, and human gene promoters including, for example, but not limited to, actin promoter, myosin promoter, hemoglobin promoter, and creatine kinase promoter. Furthermore, the application should not be limited to the use of constitutive promoters only, and inducible promoters are also contemplated herein. The use of an inducible promoter provides a molecular switch that enables expression of the polynucleotide sequence to which it is operably linked when such expression is desired and turns off expression when not desired. Inducible promoters include, but are not limited to, metallothionein promoters, glucocorticoid promoters, progesterone promoters, and tetracycline promoters.
In some embodiments, expression of the anti-FcRn antibody is inducible. In some embodiments, the nucleic acid sequence encoding an anti-FcRn antibody is operably linked to an inducible promoter, including any of the inducible promoters described herein.
Inducible promoter
The use of an inducible promoter provides a molecular switch that can initiate expression of a polynucleotide sequence operably linked thereto when expression is desired and which can shut down expression when expression is not desired. Exemplary inducible promoters suitable for use in eukaryotic cells include, but are not limited to, hormone-modulating elements (see, e.g., mader, S.and White, J.H. (1993) Proc.Natl. Acad. Sci. USA 90:5603-5607), synthetic ligand-modulating elements (see Spencer, D.M.et al (1993) Science 262:1019-1024), and ionizing radiation-modulating elements (see Manome, Y.et al (1993) Biochemistry 32:10607-10613;Datta,R.et al) (1992) Proc.Natl. Acad. Sci. USA 89:1014-10153). Other exemplary inducible promoters suitable for use in mammalian systems in vivo or in vitro are described in Gingrich et al (1998) Annual Rev. Neurosci 21:377-405. In some embodiments, the inducible promoter system for expression of the anti-FcRn antibody is the Tet system. In some embodiments, the inducible promoter system for expression of the anti-FcRn antibody is the e.
One exemplary inducible promoter system employed in this application is the Tet system. The system is based on the Tet system described by golden et al (1993). In one exemplary embodiment, the target polynucleotide is controlled by a promoter comprising one or more Tet operator (TetO) sites. In the inactive state, the Tet repressor (TetR) binds to the TetO site and inhibits transcription of the promoter. In the activated state, for example, in the presence of an inducer such as tetracycline (Tc), anhydrous tetracycline, doxycycline (Dox), or an active analog thereof, the inducer will release TetR from TetO, resulting in transcription. Doxycycline is a member of the tetracycline antibiotic family under the chemical name 1-dimethylamino-2, 4a,5, 7-pentahydroxy-11-methyl-4, 6-dioxo-1, 4a,11 a,12 a-hexahydrotetraene-3-carboxamide.
In one embodiment, tetR is codon optimized for expression in mammalian cells, such as mouse or human cells. Because of the degeneracy of the genetic code, most amino acids are encoded by more than one codon, such that the sequence of a given nucleic acid has a large number of variants without any change in the amino acid sequence encoded thereby. However, many organisms differ in codon usage, also known as "codon preference" (i.e., the preference of a given amino acid to use a particular codon). Codon preference is generally related to the presence of dominant tRNA species for a particular codon, which in turn increases the efficiency of mRNA translation. Coding sequences derived from a particular species (e.g., prokaryotes) can thus be tailored by codon optimization to enhance their expression in a different species (e.g., eukaryotes).
Other specific variations of the Tet system include the following "Tet-Off" and "Tet-On" systems. In the Tet-off system, transcription is inactive in the presence of Tc or Dox. In this system, the tetracycline-regulated transcriptional activator protein (tTA), consisting of TetR fused to the strong transcriptional activation domain of the herpes simplex virus VP16, regulates expression of the target nucleic acid under the transcriptional control of the tetracycline responsive promoter element (TRE). The TRE element consists of a TetO sequence tandem fused to a promoter (typically the smallest promoter sequence derived from the human cytomegalovirus immediate early promoter). In the absence of Tc or Dox, tTA binds to TRE and activates transcription of the target gene. In the presence of Tc or Dox, tTA cannot bind to TRE and the target gene cannot be expressed.
In contrast, in the Tet-On system, transcription is active in the presence of Tc or Dox. The Tet-On system is based On the reverse tetracycline regulated transcriptional activator rtTA. Like tTA, rtTA is a fusion protein consisting of the TetR repressor and VP16 transcriptional activation domain. However, a 4 amino acid change in the DNA binding region of TetR alters the binding properties of rtTA such that it recognizes only the tetO sequence on the target transgenic TRE in the presence of Dox. Therefore in the Tet-On system rtTA activates the transcription of the target gene regulated by TRE only in the presence of Dox.
Another inducible promoter system is the E.coli lac repressor system (see Brown et al, cell 49:603-612 (1987)). The Lac repressor system functions by regulating transcription of a polynucleotide of interest operably linked to a promoter comprising the Lac operator (lacO). Lac repressors (lacR) bind to LacO and thereby prevent transcription of the target polynucleotide. Expression of the polynucleotide of interest is induced by a suitable inducer, for example isopropyl- β -D thiogalactopyranoside (IPTG).
To assess the expression of the polypeptide or portion thereof, the expression vector to be introduced into the cell may further comprise a selectable marker gene or a reporter gene or both to facilitate identification and selection of the expressing cell from a population of cells transfected or infected with the viral vector. In other aspects, the selectable marker may be carried on separate DNA fragments and used in a co-transfection experiment. Either the selectable marker gene or the reporter gene may be flanked by appropriate regulatory sequences to enable expression in the host cell. Useful selectable markers include, for example, antibiotic resistance genes, such as neo and the like.
Reporter genes can be used to identify potentially transfected cells and evaluate the function of regulatory sequences. Typically, a reporter gene is a gene that is not present in or expressed by a recipient organism or tissue, and encodes a polypeptide whose expression is manifested by some readily detectable property, such as enzymatic activity. After the DNA is introduced into the recipient cell, the expression of the reporter gene is detected at an appropriate time. Suitable reporter genes may include genes encoding luciferases, beta-galactosidases, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or green fluorescent protein (see Ui-Tel et al 2000 FEBS Letters 479:79-82). Suitable expression systems are well known and may be prepared by known techniques or obtained commercially. In general, constructs that display the smallest 5' flanking region of the highest expression level of the reporter gene are considered promoters. Such promoter regions may be linked to reporter genes and used to assess the ability of certain substances to regulate promoter-driven transcription.
In some embodiments, nucleic acids encoding any of the full length anti-FcRn antibodies described herein are provided. In some embodiments, the nucleic acid comprises one or more nucleic acid sequences encoding a full length anti-FcRn antibody heavy and light chain. In some embodiments, each of the one or more nucleic acid sequences is contained in a separate vector. In some embodiments, at least some of the nucleic acid sequences are contained in the same vector. In some embodiments, all nucleic acid sequences are contained in the same vector. The vector may be selected from, for example, mammalian expression vectors and viral vectors (such as vectors derived from retroviruses, adenoviruses, adeno-associated viruses, herpesviruses and lentiviruses).
Methods for introducing and expressing genes into cells are known in the art. In the context of expression vectors, the vector may be readily introduced into a host cell, such as a mammalian cell, bacterial, yeast or insect cell, by any method known in the art. For example, the expression vector may be introduced into the host cell by physical, chemical or biological means.
Physical methods for introducing polynucleotides into host cells include calcium phosphate precipitation, lipofection, gene gun methods, microinjection, electroporation, and the like. Methods for preparing cells comprising vectors and/or exogenous nucleic acids are well known in the art. See, e.g., green and Sambrook (2013,Molecular Cloning:A Laboratory Manual,Cold Spring Harbor Laboratory,New York). In some embodiments, the polynucleotide is introduced into the host cell by calcium phosphate transfection.
Biological methods for introducing polynucleotides of interest into host cells include the use of DNA and RNA vectors. Viral vectors, particularly retroviral vectors, have become the most widely used method for inserting genes into mammalian cells, such as human cells. Other viral vectors may be derived from lentiviruses, poxviruses, herpes simplex virus type 1, adenoviruses, adeno-associated viruses, and the like. See, e.g., U.S. Pat. nos.5,350,674 and 5,585,362.
Chemical methods for introducing polynucleotides into host cells include colloidal dispersion systems, such as macromolecular complexes, nanocapsules, microspheres, magnetic beads, and lipid-based systems, including oil-in-water emulsions, micelles, mixed micelles, and liposomes. An exemplary colloidal system used as a delivery vehicle in vivo and in vitro is a liposome (e.g., an artificial membrane vesicle).
In the case of non-viral delivery systems, an exemplary delivery vehicle is a liposome. The use of lipid formulations to introduce nucleic acids into host cells (in vitro, ex vivo or in vivo) is contemplated. In another aspect, the nucleic acid may be conjugated to a lipid. The lipid-bound nucleic acid may be entrapped within the aqueous interior of the liposome, dispersed within the lipid bilayer of the liposome, linked to the liposome by a linking molecule that binds to the liposome and the oligonucleotide, entrapped in the liposome, formed a complex with the liposome, dispersed in a solution containing the lipid, mixed with the lipid, bound to the lipid, suspended in the lipid, contained in or mixed with the micelle, or otherwise bound to the lipid. The lipid, lipid/DNA or lipid/expression vector-related composition is not limited to any particular structure in solution. For example, they may exist in a bilayer structure, in micelles, or in a "collapsed" structure. They may also be simply dispersed in solution, possibly forming aggregates of non-uniform size or shape. Lipids are fatty substances, which may be naturally occurring or synthetic. For example, lipids include fat droplets naturally occurring in the cytoplasm, as well as a class of compounds containing long chain aliphatic hydrocarbons and derivatives thereof, such as fatty acids, alcohols, amines, amino alcohols, and aldehydes.
Regardless of the method used to introduce exogenous nucleic acid into a host cell or otherwise expose the cell to the inhibitors of the present application, various experiments can be performed in order to confirm the presence of the recombinant DNA sequence in the host cell. Such assays include, for example, "molecular biology" assays well known to those of skill in the art. Such as Southern and Northern blotting, RT-PCR and PCR; "biochemical" experiments, such as detecting the presence or absence of a particular polypeptide, such as by immunological methods (ELISAs and Western blots) or by the experiments described herein, are within the scope of the present application.
Preparation of anti-FcRn antibodies
In some embodiments, the anti-FcRn antibody is a monoclonal antibody or is derived from a monoclonal antibody. In some embodiments, the anti-FcRn antibody comprises V from a monoclonal antibody H And V L Or a variant thereof. In some embodiments, the anti-FcRn antibody further comprises CH1 and CL regions from a monoclonal antibody, or a variant thereof. Monoclonal antibodies can be prepared using methods known in the art, including hybridoma cell methods, phage display methods, or using recombinant DNA methods, for example. Furthermore, exemplary phage display methods are described herein and in the examples below.
In hybridoma cell methods, hamsters, mice, or other suitable host animals are typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, lymphocytes may be immunized in vitro. The immunizing agent may include a polypeptide or fusion protein of the protein of interest. Typically, peripheral Blood Lymphocytes (PBLs) are used if human cells are desired, whereas spleen cells or lymph node cells are used if non-human mammalian cells are desired. Lymphocytes are fused with an immortalized cell line, such as polyethylene glycol, using an appropriate fusion agent to form a hybridoma cell. Immortalized cell lines are typically transformed mammalian cells, especially myeloma cells of rodent, bovine and human origin. Rat or mouse myeloma cell lines are typically employed. The hybridoma cells may be cultured in a suitable medium, which preferably contains one or more substances that inhibit the growth or survival of the unfused immortalized cells. For example, if the parent cell lacks hypoxanthine-guanine phosphoribosyl transferase (HGPRT or HPRT), the hybridoma cell culture medium typically includes hypoxanthine, aminopterin, and thymidine (HAT medium), which prevents HGPRT-deficient cells from growing.
In some embodiments, the immortalized cell lines fuse efficiently, ensure high levels of stable expression of antibodies by the antibody-producing cell of choice, and are sensitive to certain media, such as HAT media. In some embodiments, the immortal cell line is a mouse myeloma cell line, available from, for example, the center of the Sork cell deposit in san Diego, calif., and the American type culture Collection in Marassus, virginia. Human myeloma and murine-human hybrid myeloma cell lines are also described for use in the production of humanized monoclonal antibodies.
The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the polypeptide. The binding specificity of monoclonal antibodies produced by hybridoma cells can be determined by immunoprecipitation or in vitro binding assays, such as Radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). Such techniques or analytical methods are known in the art. The binding affinity of a monoclonal antibody can be determined by, for example, the Scatchard (Scatchard) assay described in Munson and Pollard, anal. Biochem.,107:220 (1980).
After the desired hybridoma cells are identified, the target clone may be subcloned by limiting dilution and cultured by standard methods. Suitable media for this purpose include, for example, modified Eagle Medium (DMEM) and RPMI-1640 medium. Alternatively, the hybridoma cells may be grown as ascites in a mammalian body.
Monoclonal antibodies secreted by subclones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification methods, such as protein A-sepharose, hydroxyapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.
In some embodiments, according to any of the anti-FcRn antibodies described herein, the anti-FcRn antibody comprises a sequence selected from a clone of an antibody library (e.g., a phage library displaying scFv or Fab fragments). The clones may be identified by screening combinatorial libraries of antibody fragments having the desired activity. For example, a variety of methods are known in the art for generating phage display libraries and screening these libraries to obtain antibodies of the desired binding characteristics. These methods are reviewed in, for example, hoogenboom et al, methods in Molecular Biology 178:178:1-37 (O' Brien et al, ed., human Press, totowa, N.J., 2001), and in, for example, mcCafferty et al, nature 348:552-554; clackson et al, nature 352:624-628 (1991); marks et al, J.mol. Biol.222:581-597 (1992); marks and Bradbury, methods in Molecular Biology 248:161-175 (Lo, ed., human Press, totowa, n.j., 2003); sidhu et al, J.mol. Biol.338 (2): 299-310 (2004); lee et al, J.mol.biol.340 (5): 1073-1093 (2004); felloose, proc. Natl. Acad. Sci. USA 101 (34): 12467-12472 (2004); and Lee et al, J.Immunol. Methods 284 (1-2): 119-132 (2004).
In some phage display methods, V is cloned separately by Polymerase Chain Reaction (PCR) H And V L All components of the gene are randomly recombined in a phage library and then screened for phages capable of binding antigen as described in Winter et al, ann.rev.immunol.,12:433-455 (1994). Phage typically display antibody fragments as scFv fragments or as Fab fragments. The immune-derived library phage provides high affinity antibodies to the immunogen without the need to construct hybridoma cells. Alternatively, natural libraries (e.g., from humans) can be cloned to provide a single antibody source against multiple non-self and self-antigens without any immunization, as described in Griffiths et al, EMBO J,12:725-734 (1993). Finally, natural libraries can also be prepared by cloning non-rearranged V-gene fragments from stem cells and encoding CDR3 hypervariable regions using PCR primers comprising random sequences and completing the rearrangement in vitro, as described in Hoogenboom and Winter, J.mol.biol.,227:381-388 (1992). Patent publications describing human antibody phage libraries include, for example, U.Pat.Nos.5,750,373 and US Patent Publication Nos. 2005/0075974, 2005/019455, 2005/0266000, 2007/017126, 2007/0160598, 2007/027764, 2007/0292936 and 2009/0002360.
The anti-FcRn antibodies are prepared by a method of phage display screening of the anti-FcRn antibody portion of the library capable of specifically binding to the target FcRn. The library may be a human scFv phage display library having at least 1X 10 9 (e.g. at least 1X 10) 9 、2.5×10 9 、5×10 9 、7.5×10 9 、1×10 10 、2.5×10 10 、5×10 10 、7.5×10 10 Or 1X 10 11 ) A diverse variety of unique human antibody fragments. In some embodiments, the library is a human natural library constructed from DNA extracted from PMBCs and spleen of healthy subjects, comprising all human heavy and light chain subfamilies. In some embodiments, the library is a human natural library constructed from DNA extracted from PMBCs isolated from patients with various diseases, such as patients with autoimmune diseases, cancer patients, and patients with infectious diseases. In some embodiments, the library is a semi-synthetic human library in which the heavy chain CDR3 is entirely random, with all amino acids (except cysteine) present at any given position with the same probability. (see, e.g., hoet, R.M. et al, nat. Biotechnol.23 (3): 344-348, 2005). In some embodiments, the heavy chain CDR3 of the semisynthetic human library is between 5 and 24 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
15. 16, 17, 18, 19, 20, 21, 22, 23, or 24) amino acids. In some embodiments, the library is a fully synthetic phage display library. In some embodiments, the library is a non-human phage display library.
Phage clones with high affinity for the target FcRn may be screened by iterative binding of phage to the target FcRn, which is bound to a solid support (e.g., beads for solution panning or mammalian cells for cell panning), followed by removal of unbound phage and elution of specifically bound phage. The bound phage clones are then eluted and used to infect appropriate host cells, e.g., E.coli XL1-Blue, for expression and purification. Phage clones that specifically bind FcRn can be enriched by multiple rounds of panning (e.g., 2, 3, 4, 5, 6 or more rounds), such as solution panning, cell panning, or both. Specific binding of the enriched phage clones to the target FcRn can be detected by any method known in the art, including, for example, ELISA and FACS.
Another method of screening antibody libraries is to display proteins on the surface of yeast cells. Wittrup et al (U.S. Pat. Nos. 6,699,658 and 6,696,251) developed a method for displaying libraries of yeast cells. In this yeast display system, one component comprises a yeast lectin protein (Aga 1) anchored to the yeast cell wall, and the other component comprises a second subunit of lectin protein Aga2, which subunit can bind to the Aga1 protein via disulfide bonds and thus be displayed on the yeast cell surface. The Aga1 protein is expressed by integrating the Aga1 gene into the yeast chromosome. A library of single-chain variable fragments (scFv) was fused to the Aga2 gene in a yeast display plasmid, and after transformation, the library was retained in the yeast due to the presence of additional nutritional markers. Both the Aga1 and Aga2 proteins are expressed under the control of a galactose-inducible promoter.
Human antibody V gene bank (V) H And V K Fragments) were obtained by PCR methods using a set of degenerate primers (Sblatttero, D.and Bradbury, A.Immunotechnology 3,271-278 1998). PCR templates were derived from commercially available RNA or cDNA, including PBMC, spleen, lymph nodes, bone marrow and tonsils. Will be independent V H And V K After PCR library pooling, they were assembled into scFv forms by overlap extension PCR (Sheets, M.D.et al, proc.Natl. Acad.Sci.USA 95,6157-6162 1998). To construct a yeast scFv display library, the resulting scFv PCR product was cloned into a yeast display plasmid in yeast by homologous recombination. (Chao, G, et al, nat Protoc.2006;1 (2): 755-68.Miller KD,et al.Current Protocols in Cytometry 4.7.1-4.7.30,2008).
anti-FcRn antibodies can be screened using a mammalian cell display system, wherein the antibody is partially displayed on the cell surface and antibodies specifically targeting FcRn are isolated by antigen-directed screening methods (as described in U.S. patent No.7,732,195B2). A Chinese Hamster Ovary (CHO) cell library displaying a large number of human IgG antibody genes can be established and used to discover clones expressing high affinity antibody genes. Another display system has been developed that allows the same protein to be displayed and secreted simultaneously on the cell surface by alternative splicing, wherein the displayed protein phenotype remains genotype-dependent, allowing the secreted soluble antibody to be characterized simultaneously in biophysical and cell function-based assays. This method overcomes many of the limitations previously exhibited by mammalian cells and enables direct screening and maturation of antibodies in the form of full-length, glycosylated IgGs (Peter M.Bowers, et al Methods 2014, 65:44-56). Transient expression systems are suitable for single round antigen selection prior to antibody gene recovery and are therefore most useful for selecting antibodies from smaller libraries. Stable exon vectors offer an attractive option. The exon vectors can be transfected efficiently and stably maintained at low copy numbers, allowing multiple rounds of panning and resolution of more complex antibody libraries.
The IgG library was constructed based on ligation of germline sequence V gene segments isolated from a population of human donors with rearranged (D) J regions. Reverse transcription of RNA collected from 2000 human blood samples into cDNA using V H And V K Specific primer amplification V H And V K Fragments were purified by gel extraction. Will V H And V K Fragments were subcloned into display vectors containing the IgG1 or K constant regions, respectively, and then 293T was electroporated or transduced into cells to prepare IgG libraries. To prepare scFv antibody display libraries, ligation V H And V K To generate scfvs, which are then subcloned into display vectors and electroporated or transduced into 293T cells. It is well known that IgG libraries are constructed based on germline sequence V gene segments and rearranged (D) J regions isolated from a population of donors, which may be mice, rats, rabbits or monkeys.
Monoclonal antibodies can also be prepared by recombinant DNA methods, for example as described in U.S. patent No.4,816,567. The DNA encoding the monoclonal antibodies described herein can be readily isolated and sequenced by conventional methods, such as by oligonucleotide probes that specifically bind to the light and heavy chain genes encoding murine antibodies. Hybridoma cells as described above or FcRn-specific phage clones of the present application can serve as a source of such DNA. After isolation, the DNA may be placed in an expression vector, which is then transfected into a host cell, such as simian COS cells, chinese hamster ovary Cancer (CHO) cells, or myeloma cells that do not produce immunoglobulins, to obtain monoclonal antibodies synthesized in the recombinant host cell. The DNA may also be modified, for example by replacing the human heavy and light chain constant regions with coding sequences and/or by replacing homologous non-human sequences with framework regions (U.S. patent No.4,816,567; morrison et al, supra), or by covalently joining all or part of the coding sequence of an immunoglobulin to the coding sequence of a non-immunoglobulin polypeptide. Such non-immunoglobulin polypeptides may replace the constant regions of the antibodies herein, or may replace one of the antigen binding sites in the variable domains of the antibodies herein, to form chimeric bivalent antibodies.
The antibody may be a monovalent antibody. Methods of making monovalent antibodies are known in the art. For example, a recombinant expression method involving an immunoglobulin light chain and a modified heavy chain. Heavy chains are typically truncated at any position in the Fc region to prevent heavy chains from cross-linking with each other. Alternatively, the relevant cysteine residues are substituted with other amino acid residues or deleted to prevent cross-linking.
In vitro methods are also suitable for the preparation of monovalent antibodies. Digestion of antibodies to produce antibody fragments, particularly Fab fragments, may be accomplished using any method known in the art.
The antibody variable domain having the desired binding specificity (antibody-antigen binding site) may be fused to an immunoglobulin constant region. Preferably fusion with an immunoglobulin heavy chain constant region, which comprises at least part of the hinge, CH2 and CH3 regions. In some embodiments, the first heavy chain constant region (CH 1) comprising the necessary site for light chain binding is present in at least one fusion. The DNA encoding the immunoglobulin heavy chain fusion, and if desired, the immunoglobulin light chain, is inserted into a separate expression vector and co-transfected into a suitable host organism.
Fully human and humanized antibodies
The anti-FcRn antibody (e.g., full length anti-FcRn antibody) may be a fully human antibody or a humanized antibody. Humanized forms of non-human (e.g., mouse) antibody portions are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (e.g., fv, fab, fab ', F (ab') 2 Other antigen binding subsequences of scFv or antibodies), which typically include minimal sequences derived from non-human immunoglobulins. Humanized antibodies include human immunoglobulins, immunoglobulin chains or fragments thereof (recipient antibodies) in which residues from a recipient CDR are replaced by non-human (donor antibody) CDR residues having the desired specificity, affinity and properties, such as mouse, rat or rabbit CDRs. In some embodiments, the human immunoglobulin Fv framework region residues are replaced by corresponding non-human residues. Humanized antibodies may also comprise amino acid residues that are neither of the recipient antibody nor in the introduced CDR or framework sequences. Typically, a humanized antibody comprises at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are human immunoglobulin consensus sequences.
Typically, humanized antibodies contain one or more amino acid residues introduced from a non-human source. Those non-human amino acid residues are often referred to as "import" residues, typically from "import" variable domains. According to some embodiments, humanization may be performed essentially as described below by Winter and colleagues (Jones et al, nature,321:522-525 (1986); riechmann et al, nature,332:323-327 (1988); verhoeyen et al, science,239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Thus, this "humanized" antibody portion (U.S. patent No.4,816,567), which is substantially less than a fully human antibody, has its variable domains replaced by corresponding sequences from a non-human source. In practice, humanized antibody portions are typical human antibody portions in which some CDR residues and possibly some framework region residues are replaced with residues from similar sites in rodent antibodies.
Fully human antibodies are an alternative to humanization. For example, transgenic animals (e.g., mice) that are capable of producing a complete fully human antibody library after immunization without endogenous immunoglobulin production can now be prepared. For example, homozygous deletion of the antibody heavy chain Junction (JH) gene in chimeric and germ-line mutant mice has been reported to completely suppress endogenous antibody production. Transferring an array of human germline immunoglobulin genes into such germline mutant mice, human antibodies can be produced under antigen stimulation, see, e.g., akobovits et al, PNAS USA,90:2551 (1993); jakobovits et al, nature,362:255-258 (1993); bruggemann et al, year in immunol.,7:33 (1993); U.S. patent nos.5,545,806,5,569,825,5,591,669,5,545,807; and WO 97/17852. Alternatively, fully human antibodies can be prepared by introducing a human immunoglobulin locus into a transgenic animal (e.g., a mouse in which endogenous immunoglobulin genes have been partially or fully silenced). Upon antigen stimulation, the production of fully human antibodies can be found to be very similar in all respects to their production in humans, including gene rearrangement, assembly and antibody libraries. Such methods are described, for example, in U.S. patent nos.5,545,807;5,545,806;5,569,825;5,625,126;5,633,425; and 5,661,016,and Marks et al, bio/Technology,10:779-783 (1992); lonberg et al, nature,368:856-859 (1994); morrison, nature,368:812-813 (1994); fishwild et al Nature Biotechnology,14:845-851 (1996); neuberger, nature Biotechnology,14:826 (1996); lonberg and Huszar, international.Rev.Immunol., 13:65-93 (1995).
Fully human antibodies are also produced by in vitro activation of B cells (see U.S. patents 5,567,610 and 5,229,275) or by using various techniques known in the art, including phage display libraries. Hoogenboom and Winter, J.mol.biol.,227:381 (1991); the techniques of Marks et al, J.mol.biol.,222:581 (1991), cole et al, and Boerner et al can also be used to prepare fully human monoclonal antibodies. See Cole et al, monoclonal Antibodies and Cancer Therapy, alan R.Lists, p.77 (1985) and Boerner et al, J.Immunol.,147 (1): 86-95 (1991).
anti-FcRn antibody variants
In some embodiments, the amino acid sequences of anti-FcRn antibody variants provided herein (e.g., full length anti-FcRn antibodies) are also contemplated. For example, it may be desirable to improve the binding affinity and/or other biological activity of antibodies. The amino acid sequence of an antibody variant may be prepared by introducing appropriate modifications in the nucleotide sequence encoding the antibody or by peptide synthesis. Such modifications include, for example, deletions and/or insertions and/or substitutions of residues in the amino acid sequence of the antibody. The final construction can be accomplished by any combination of amino acid residue deletions, insertions, and substitutions to impart the desired characteristics. For example, antigen binding.
In some embodiments, anti-FcRn antibody variants having one or more amino acid substitutions are provided. Target sites for substitution mutations include hypervariable regions (HVRs) and Framework Regions (FRs). Amino acid substitutions may be introduced into the antibody of interest to screen for products of a desired activity, e.g., improved biological activity, retention/improvement of antigen binding capacity, reduced immunogenicity, or improved ADCC or CDC.
Conservative substitutions are shown in table 4 below.
TABLE 4 conservative substitutions
Original residue Exemplary substitution Preferably substituted
Ala(A) Val；Leu；Ile Val
Arg(R) Lys；Gln；Asn Lys
Asn(N) Gln；His；Asp,Lys；Arg Gln
Asp(D) Glu；Asn Glu
Cys(C) Ser；Ala Ser
Gln(Q) Asn；Glu Asn
Glu(E) Asp；Gln Asp
Gly(G) Ala Ala
His(H) Asn；Gln；Lys；Arg Arg
Ile(I) Leu；Val；Met；Ala；Phe；Norleucine Leu
Leu(L) Norleucine；Ile；Val；Met；Ala；Phe Ile
Lys(K) Arg；Gln；Asn Arg
Met(M) Leu；Phe；Ile Leu
Phe(F) Trp；Leu；Val；Ile；Ala；Tyr Tyr
Pro(P) Ala Ala
Ser(S) Thr Thr
Thr(T) Val；Ser Ser
Trp(W) Tyr；Phe Tyr
Tyr(Y) Trp；Phe；Thr；Ser Phe
Val(V) Ile；Leu；Met；Phe；Ala；Norleucine Leu
Amino acids are classified into different classes according to the nature of the side chain:
a. hydrophobic amino acid: norleucine Norleucone, methionine Met, alanine Ala, valine
Val, leucine Leu, isoleucine Ile;
b. neutral hydrophilic amino acid: cysteine Cys, serine Ser, threonine Thr, asparagine
Asn, glutamine Gln;
c. acidic amino acid: aspartic acid Asp, glutamic acid Glu;
d. basic amino acid: histidine His, lysine Lys, arginine Arg;
e. contains amino acids affecting the chain direction: glycine Gly, proline Pro;
f. aromatic amino acid: tryptophan Trp, tyrosine Tyr, phenylalanine Phe.
Substitutions of non-conservative amino acids include substitution of one of the above classes into another class.
One exemplary substitution variant is an affinity matured antibody, conveniently produced using, for example, phage display-based affinity maturation techniques. Briefly, one or more CDR residues are mutated, the variant antibody portion is displayed on a phage, and variants are screened for a particular biological activity (e.g., biological activity or binding affinity based on IgG cycling experiments). Alterations (e.g., substitutions) may be made in the HVRs regions to obtain improved biological activity or binding affinity based on IgG cycling experiments. The binding affinities of the resulting variants VH and VL may be measured at "hot spot" of the HVR, i.e. at codon-encoded residues that undergo high frequency mutations during somatic maturation (see, e.g., chordhury, methods mol. Biol.207:179-196 (2008)), and/or at Specific Determinant Residues (SDRs). Methods of constructing and reselecting affinity maturation from secondary libraries have been described in several documents, for example, hoogenboom et al in Methods in Molecular Biology 178:1-37 (O' Brien et al ed., human Press, totowa, N.J. (2001)).
In some affinity maturation embodiments, diversity is introduced into the selected variable genes for affinity maturation by any of a variety of methods (e.g., error-prone PCR, strand shuffling, or oligonucleotide-directed mutagenesis). A secondary library is then created. The library is screened to identify antibody variants with the desired affinity. Another approach to introducing diversity involves HVR-mediated approaches in which several HVR residues (e.g., 4-6 residues at a time) are randomized. HVR residues involved in antigen binding are specifically recognized, for example, using alanine scanning mutagenesis or modeling. CDR-H3 and CDR-L3 regions are generally particularly important targets.
In some embodiments, substitutions, insertions, or deletions may occur within one or more HVRs, provided that such changes do not substantially reduce the ability of the antibody to bind to an antigen. For example, conservative changes (e.g., conservative substitutions provided herein) may be made in HVRs that do not substantially reduce binding affinity. These changes may occur outside the HVR "hot spot" or SDRs region. Variant V provided above in some embodiments H And V L The sequence, each HVR is either unchanged or contains no more than 1, 2, or 3 amino acid substitutions.
One useful method by which amino acid residues or regions of an antibody can be identified that can be targeted for mutation is termed "alanine scanning mutagenesis" as described in Cunningham and Wells (1989) Science, 244:1081-1085. In this method, one or a group of target residues (e.g., charged residues such as arginine, aspartic acid, histidine, lysine, and glutamic acid) are substituted with neutral or negatively charged amino acids (e.g., alanine or glutamic acid) to determine whether the interaction of the antibody with the antigen is affected. Substitutions may be further introduced at the amino acid position to demonstrate functional sensitivity of the position to the initial substitution. Alternatively or additionally, the contact site between the antibody and the antigen is identified by the crystal structure of the antigen-antibody complex. These contact site residues and adjacent residues may be targeted or eliminated as substitution candidates. Variants are screened to determine if they have the desired properties.
Insertion of amino acid sequences, including fusion at the amino and/or carboxy terminus, ranges in length from 1 residue to polypeptides comprising 100 or more residues, and also includes insertion of 1 or more amino acid residues within the sequence. Examples of terminal insertions include antibodies having a methionyl residue at the N-terminus. Other insertional variants of antibody molecules include polypeptides that fuse an enzyme (e.g., ADEPT) or increase the serum half-life of an antibody at the N-or C-terminus of the antibody molecule.
Variant Fc region
In some embodiments, one or more amino acid modifications are introduced into the Fc region of an antibody described herein (e.g., a full length anti-FcRn antibody or anti-FcRn antibody fusion protein), thereby producing an Fc region variant. In some embodiments, the Fc region variant has enhanced ADCC potency, typically associated with Fc-binding receptors (FcRs). In some embodiments, the Fc region variant has reduced ADCC potency. There are many examples of alterations or mutations in Fc sequences affecting their potency, for example, WO 00/42072 and Shields et al J biol. Chem.9 (2): 6591-6604 (2001) describe antibody variants with increased or decreased binding to FcRs. The contents of these publications are incorporated herein by reference.
Antibody-dependent cell-mediated cytotoxicity (ADCC) is the mechanism of action of therapeutic antibodies against tumor cells. ADCC is a cell-mediated immune defense in which effector cells of the immune system actively lyse target cells (e.g., cancer cells) when antigens on the surface of the target cell membrane are bound by specific antibodies (e.g., anti-FcRn antibodies). Typically ADCC effects involve NK cells activated by antibodies. NK cells express the Fc receptor CD16. The receptor recognizes and binds to the Fc portion of an antibody molecule that binds to the surface of a target cell. The most common Fc receptor on the surface of NK cells is CD16 or fcyriii. Binding of the Fc receptor to the Fc region of the antibody results in activation of NK cells, releasing the cell lysis particles, followed by apoptosis of the target cells. The killing of tumor cells by ADCC can be determined by experiments specific for NK-92 cells transfected with high affinity FcR. The results were compared with wild-type NK-92 which did not express FcR.
In some embodiments, the present application also provides anti-FcRn antibody variants (e.g., full length anti-FcRn antibody variants) comprising an Fc region having a portion but not all of the effector function such that it has an extended half-life in vivo, yet the specific effector function (e.g., CDC or ADCC) is not necessary or detrimental, which is a desirable candidate for the present application. Reduction/elimination of CDC and/or ADCC activity is confirmed by cytotoxicity assays in vitro and/or in vivo. For example, antibodies were confirmed to lack fcγr binding capacity (and thus potentially ADCC activity) by an Fc receptor (FcR) binding assay but still retain FcRn binding capacity. Among the major cells mediating ADCC, NK cells express fcyriii only, whereas monocytes express fcyri, fcyrii and fcyriii. The expression of FcR on hematopoietic cells is summarized in Table 3 at page 464 of Ravetch and Kinet Annu.Rev.Immunol.9:457-492 (1991). Non-limiting examples of in vitro evaluation of ADCC activity of a target molecule are described in U.S. Pat. No.5,500,362 (see, e.g., hellstrom, I.et al Proc.Nat 'l Acad.Sci.USA 83:7059-7063 (1986) and Hellstrom, I.et al., proc.Nat' l Acad.Sci.USA 82:1499-1502 (1985); U.S. Pat. No.5,821,337 (see, e.g., buggemann, M.et., J.exp.Med.166:1351-1361 (1987)) or non-radioactive detection methods may be employed (see, e.g., ACTI) TM Flow cytometry non-radioactive cytotoxicity assays (CellTechnology, inc.Mountain View, calif.) and CYTOTOX 96 TM Nonradioactive cytotoxicity assay (Promega, madison, wis.). Effector cells employed in such assay experiments include Peripheral Blood Mononuclear Cells (PBMCs) and natural killer cells (NK). Alternatively, or in addition, ADCC activity of the target molecule is detected in vivo, e.g., in an animal model, such as ClyneAs described in s et al Proc. Nat' l Acad. Sci. USA 95:652-656 (1998). Also, a C1q binding assay may be performed to confirm that the antibody is unable to bind to C1q, thereby lacking CDC activity. See, e.g., C1q and C3C binding ELISA in WO 2006/029879 and WO 2005/100402. To assess complement activation, CDC assays can be performed (see, e.g., gazzano-Santoro et al, J.Immunol. Methods 202:163 (1996); cragg, M.S. et al, blood 101:1045-1052 (2003); and Cragg, M.S. and M.J. Glennie, blood 103:2738-2743 (2004)). FcRn binding and in vivo clearance/half-life are determined using methods known in the art (see, e.g., petkova, s.b. et al, int' l.immunol.18 (12): 1759-1769 (2006)).
Antibodies with reduced effector function comprising substitution of one or more residues at residues 238, 265, 269, 270, 297, 327 and 329 of the Fc region (u.s.pat.no. 6,737,056). These Fc variants include Fc variants with substitution of two or more residues at positions 265, 269, 270, 297 and 327, including Fc variants known as "DANA" with substitution of alanine at residues 265 and 297 (u.s.pat. No.7,332, 581).
Such antibody variants with increased or decreased binding to FcRs have been described (see, e.g., U.S. Pat.No.6,737,056; WO 2004/056312, and Shields et al, J.biol.chem.9 (2): 6591-6604 (2001)).
In some embodiments, an anti-FcRn antibody (e.g., full length anti-FcRn antibody) variant is provided comprising an Fc region variant having one or more amino acid substitutions capable of enhancing ADCC effects. In some embodiments, the Fc region variant comprises one or more amino substitutions at positions 298, 333, and/or 334 (EU residue numbering) of the Fc region that are capable of enhancing ADCC effects. In some embodiments, the anti-FcRn antibody (e.g., full length anti-FcRn antibody) variant includes amino acid substitutions at positions S298A, E333A, and K334A of the Fc region.
In some embodiments, the alteration of the Fc region results in an alteration (i.e., an increase or decrease) in C1q binding and/or Complement Dependent Cytotoxicity (CDC), as described in U.S.Pat.No.6,194,551, WO/51642, and Idusogie et al, J.Immunol.164:4178-4184 (2000).
In some embodiments, an anti-FcRn antibody (e.g., a full length anti-FcRn antibody) variant is provided comprising an Fc region variant having one or more amino acid substitutions capable of extending half-life or enhancing binding to an Fc receptor (FcRn). Antibodies with extended half-life and improved FcRn binding are described in US 2005/0014934A1 (hiton et al). These antibody Fc regions comprise one or more amino acid substitutions that enhance the binding of the Fc region to FcRn. These Fc variants comprise one or more substitutions in residues 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434 in the Fc region, for example a substitution in residue 434 in the Fc region (u.s.pat. No.7,371,826).
See also Duncan & Winter, nature 322:738-40 (1988); U.S. Pat. nos. 5,648,260; examples of other Fc region variants are provided in U.S. Pat. No.5,624,821 and WO 94/29351.
The present application contemplates anti-FcRn antibodies (e.g., full length anti-FcRn antibodies) comprising any one or a combination of the Fc variants described herein.
Glycosylation variants
In some embodiments, an anti-FcRn antibody provided herein (e.g., a full length anti-FcRn antibody) is altered to increase or decrease the degree of glycosylation of the anti-NGF antibody. The addition or deletion of glycosylation sites on anti-FcRn antibodies may be conveniently accomplished by altering the amino acid sequence of the anti-NGF antibody or polypeptide portion thereof to thereby add or remove one or more glycosylation sites.
Wherein the anti-FcRn antibody comprises an Fc region to which a saccharide can be altered. Natural antibodies produced by mammalian cells typically comprise branched double-antennary oligosaccharides, which are typically linked to the Fc region CH2 domain Asn297 via an N-linkage, see, e.g., wright et al, TIBTECH 15:26-32 (1997). The oligosaccharides may comprise a variety of sugars, such as mannose, N-acetylglucosaminide (GlcNAc), galactose and sialic acid, as well as trehalose attached to the GlcNAc of the "stem" of the double-antennary oligosaccharide structure. In some embodiments, the anti-FcRn antibodies of the present application may be oligosaccharide modified to produce anti-FcRn antibody variants with certain improved properties.
N-glycans attached to the CH2 domain of the Fc region are heterogeneous. Antibodies or Fc fusion proteins produced in CHO cells are fucosylated by fucosyltransferase activity, see Shoji-Hosaka et al, J.biochem.2006,140:777-83. Typically, a small fraction of naturally occurring nonfucosylated IgGs can be detected in human serum. N-glycosylation of the Fc region is important for its binding to fcγr; whereas non-fucosylated N-glycans enhance the binding capacity of Fc to fcγriiia. Enhanced binding to FcRIIIa results in enhanced ADCC effect, which is advantageous in certain antibody therapeutic applications requiring cytotoxicity.
In some embodiments, enhanced effector function may be detrimental when Fc-mediated cellular cytotoxicity is not required. In some embodiments, the Fc fragment or CH2 domain is non-glycosylated. In some embodiments, glycosylation is prevented by mutating the N-glycosylation site in the CH2 domain.
In some embodiments, anti-FcRn antibody (e.g., full length anti-FcRn antibody) variants are provided that comprise an Fc region, wherein the saccharide structure linked to the Fc region has reduced fucose or lacks fucose, which may enhance ADCC function. In particular, provided herein are anti-FcRn antibodies having reduced fucose relative to the same anti-FcRn antibodies produced by wild-type CHO cells. That is, they are characterized by having a smaller amount of fucose than antibodies produced by natural CHO cells (e.g., CHO cells producing a naturally glycosylated form, CHO cells containing the natural FUT8 gene). In some embodiments, the N-linked glycans of the anti-FcRn antibody have less than 50%, 40%, 30%, 20%, 10% or 5% fucose. For example, the anti-FcRn antibody may have a fucose content of 1% -80%, 1% -65%, 5% -65% or 20% -40%. In some embodiments, the N-linked glycans of the anti-FcRn antibody do not comprise fucose, i.e., wherein the anti-FcRn antibody is completely free of fucose, or is free of fucose or is defucosylated. The fucose content is determined by calculating the average fucose content in the sugar chains attached to Asn297 relative to the total amount of all sugar structures attached to Asn297 (e.g. complex, hybrid or mannose structures) as measured by MALDI-TOF mass spectrometry, as described in WO 2008/077546. Asn297 refers to the asparagine residue at position 297 of the Fc region (EU Fc region residue numbering system). However, asn297 may also be located upstream or downstream of position 297 by ±3 amino acids, i.e. between positions 294 and 300, due to minor sequence variations of the antibody. These fucosylated variants may have enhanced ADCC function. See, for example, US Patent Publication nos. US 2003/0157108 (Presta, l.), US 2004/0093621 (Kyowa Hakko Kogyo co., ltd). Examples of publications related to antibody variants that are "defucosylated" or "lack of fucose" include US 2003/0157108; WO 2000/61739; WO 2001/29246; US 2003/015614; US 2002/0164328; US 2004/0093621; US 2004/013321; US 2004/010704; US 2004/0110282; US 2004/0109865; WO 2003/085119; WO 2003/084570; WO 2005/035586; WO 2005/035778; WO 2005/053742; WO 2002/031140; okazaki et al J.mol.biol.336:1239-1249 (2004); yamane-Ohnuki et al Biotech.Bioeng.87:614 (2004). Cell lines capable of producing defucosylated antibodies include Lec13CHO cells lacking the fucosylation function of the protein (Ripka et al, arch. Biochem. Biophysis. 249:533-545 (1986), US Pat Appl No US 2003/0157108 A1,Presta,L, and WO 2004/056312 A1,Adams et al, especially example 11), and knockout cell lines, such as alpha-1, 6-fucosyltransferase genes, FUT8 knockout CHO cells (see Yamane-Ohnuki et al, biotech. Bioeng.87:614 (2004), kanda, y. Et al, biotechnol. Bioeng.,94 (4): 680-688 (2006), and WO 2003/085107).
Variants of anti-FcRn antibodies (e.g., full length anti-FcRn antibodies) further provide bisecting oligosaccharides, e.g., wherein the double antennary oligosaccharide linked to the Fc region of the anti-FcRn antibody is bisected by GlcNAc. Such anti-FcRn antibody (e.g., full length anti-FcRn antibody) variants may have reduced fucosylation and/or enhanced ADCC function. Examples of such antibody variants are described in WO 2003/011878 (Jean-mair et al); U.S. Pat. No.6,602,684 (Umana et al); US 2005/0123946 (Umana et al), and Ferrara et al Biotechnology and Bioengineering,93 (5): 851-861 (2006). Also provided are anti-FcRn antibody (e.g., full length anti-FcRn antibodies) variants having at least one galactose residue in the oligosaccharide attached to the Fc region. Such anti-FcRn antibody variants may have enhanced CDC function. Such variants are described, for example, in WO 1997/30087 (Patel et al); WO 1998/58964 (Raju, s.); and WO 1999/22764 (Raju, S.).
In some embodiments, the anti-FcRn antibody (e.g., full length anti-FcRn antibody) variant comprises an Fc region capable of binding to fcyriii. In some embodiments, the anti-FcRn antibody (e.g., full length anti-FcRn antibody) variant comprising an Fc region has ADCC activity in the presence of human effector cells (e.g., T cells) or has enhanced ADCC activity in the presence of human effector cells compared to an otherwise identical anti-FcRn antibody (e.g., full length anti-FcRn antibody) having a human wild-type IgG1Fc region.
Cysteine engineered variants
In some embodiments, it is desirable to prepare cysteine engineered anti-FcRn antibodies (e.g., full length anti-FcRn antibodies) in which one or more amino acid residues are substituted with cysteine residues. In some embodiments, the substitution residue occurs at an accessible site of the anti-FcRn antibody. By substituting those residues with cysteines, active sulfhydryl groups are located at accessible sites of anti-FcRn antibodies, which can be used to conjugate the anti-FcRn antibodies with other moieties, such as a drug moiety or linker-drug moiety, to prepare anti-FcRn immunoconjugates as further described herein. Cysteine engineered anti-FcRn antibodies (e.g., full length anti-FcRn antibodies) can be prepared as described, for example, in u.s.pat.no.7,521,541.
Derivatives and their use as inhibitors of viral infection
In some embodiments, an anti-FcRn antibody provided herein (e.g., a full length anti-FcRn antibody) may be further modified to include other non-protein portions known and readily available in the art. Suitable moieties for derivatizing anti-FcRn antibodies include, but are not limited to, water-soluble polymers. Non-limiting examples of water soluble polymers include, but are not limited to, polyethylene glycol (PEG), ethylene glycol/propylene glycol copolymers, carboxymethyl cellulose, dextran, polyvinyl alcohol, polyvinylpyrrolidone, poly-1, 3-dioxolane, poly-1, 3, 6-trioxane, ethylene/maleic anhydride copolymers, polyaminoacids (homo-or random copolymers), dextran or poly (n-vinylpyrrolidone) polyethylene glycol, propylene glycol homopolymers, propylene oxide/ethylene oxide copolymers, polyoxyethylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof. Polyethylene glycol propionaldehyde has advantages in manufacturing due to its stability in water. The polymer may have any molecular weight and may be branched or unbranched. The number of polymers attached to the anti-FcRn antibody may vary, and if more than one polymer is attached, they may be the same or different molecules. In general, the amount and/or type of polymer used for derivatization may be determined based on considerations including, but not limited to, the need to improve the properties or function of the anti-FcRn antibody, whether the anti-FcRn antibody derivative is used for treatment under particular conditions, and the like.
Pharmaceutical composition
Also provided herein are compositions (e.g., pharmaceutical compositions, also referred to herein as formulations) comprising any one of the anti-FcRn antibodies (e.g., full length anti-FcRn antibodies), nucleic acids encoding antibodies, vectors comprising nucleic acids encoding antibodies, or host cells comprising nucleic acids or vectors described herein. In some embodiments, a pharmaceutical composition is provided comprising any of the anti-FcRn antibodies described herein and a pharmaceutically acceptable carrier.
Suitable anti-FcRn antibody formulations may be prepared in lyophilized or liquid formulation form by mixing an anti-FcRn antibody of the desired purity with an optional pharmaceutically acceptable carrier, excipient or stabilizer (Remington's Pharmaceutical Sciences 16th edition,Osol,A.Ed. (1980)). Acceptable carriers, excipients, or stabilizers are non-toxic to the recipient at the dosages and concentrations employed, and include buffers such as: phosphates, citric acid, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (e.g. octadecyldimethylbenzyl ammonium chloride, hexamethyl ammonium chloride, benzalkonium chloride, benzethonium chloride, phenol, butanol or benzyl alcohol, alkyl p-hydroxybenzoates, such as methyl or propyl p-hydroxybenzoate, o-benzene Diphenols; resorcinol; cyclohexanol; 3-pentanol and m-cresol); a low molecular weight (less than 10 residues) polypeptide; proteins, such as serum albumin, gelatin or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars, such as sucrose, mannitol, trehalose, or sorbitol; salt-forming counterions such as sodium; metal complexes (e.g., zinc-protein complexes); and/or nonionic surfactants such as TWEEN TM ，PLURONICS TM Or polyethylene glycol (PEG); exemplary formulations are as described in WO98/56418 and are expressly incorporated herein by reference. Lyophilized formulations suitable for subcutaneous administration are described in WO 97/04801. Such lyophilized formulations can be reconstituted into high protein concentration formulations by means of a suitable diluent and the reconstituted formulations can be administered to the individual to be treated herein by means of subcutaneous administration. Cationic liposomes or liposomes can be used to deliver the anti-FcRn antibodies herein to cells.
The formulations described herein may contain, in addition to an anti-FcRn antibody (e.g., a full length anti-FcRn antibody), one or more additional active agents necessary for the treatment of a particular disorder, preferably agents that are complementary in activity and do not adversely affect each other. For example, in addition to anti-FcRn antibodies, it may be desirable to further include monoclonal antibody therapies for the treatment of immune-mediated diseases, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, inhibitors of the complement system, immunosuppressants, immunomodulators, or combinations thereof. These molecules are present in combination in amounts effective for the intended purpose. The effective amount of the other substances depends on the amount of anti-FcRn antibody in the formulation, the type of disease or disorder or treatment, and other factors as described above. These drugs are typically used at the same dosages and routes of administration as described herein, or at 1% to 99% of the presently employed dosages.
The anti-FcRn antibodies (e.g., full length anti-FcRn antibodies) may also be embedded in microcapsules prepared, for example, by coacervation techniques and interfacial polymerization, such as hydroxymethylcellulose or gelatin-microcapsules and poly (methyl methacrylate) microcapsules, respectively, in colloidal drug delivery systems (e.g., liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules) or in macroemulsions. Can be prepared into sustained release preparation.
Sustained release formulations of anti-FcRn antibodies (e.g., full length anti-FcRn antibodies) can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody (or fragments thereof), which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (e.g., poly (2-hydroxyethyl methacrylate) or poly (vinyl alcohol)), polylactic acid (U.S. Pat. No.3,773,919), L-glutamic acid and L-ethyl glutamate copolymers, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as LUPRON deptatm (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprorelin acetate), and poly-D (-) -3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic-glycolic acid can allow release of molecules for more than 100 days, certain hydrogels can release proteins in a shorter time. When encapsulated antibodies stay in the body for a long period of time, they may denature or aggregate as a result of exposure to a humid environment at 37 ℃ and may result in loss of biological activity or altered immunogenicity. anti-FcRn antibodies can be stabilized by rational strategies based on the respective mechanisms. For example, if the aggregation mechanism is found to be the formation of intermolecular S-S bonds through thio-disulfide interchange, stabilization may be achieved by modifying sulfhydryl residues, lyophilizing in acidic solutions, controlling water content, using appropriate additives, and developing specific polymer matrix compositions.
In some embodiments, the anti-FcRn antibody (e.g., full length anti-FcRn antibody) is formulated in a buffer containing citrate, sodium chloride, acetate, succinate, glycine, polysorbate 80 (tween 80), or any combination of the above.
Formulations for in vivo administration must be sterile. This can be easily achieved by, for example, filtration using sterile filtration membranes.
Methods of treatment using anti-FcRn antibodies
anti-FcRn antibodies (e.g., full length anti-FcRn antibodies) and/or compositions described herein can be administered to an individual (e.g., a mammal, such as a human) to promote clearance of subject autoantibodies, inhibit presentation of subject antigens, block immune responses (e.g., block activation of immune response by a subject based on immune complexes), treat an immunological disease (e.g., autoimmune disease) and an inflammatory disease in a subject. Autoimmune diseases refer to a class of diseases in which a subject's autoantibodies react with host tissue, or immune effector T cells spontaneously react to endogenous self-peptides and cause tissue destruction. Thus, the immune response is directed against the subject's own antigen (referred to as a self-antigen). By "self-antigen" is meant an antigen of normal host tissue. Normal host tissue does not include tumor cells. Such diseases include, but are not limited to, myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, guillain-barre syndrome, lupus, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, rheumatoid arthritis, systemic lupus erythematosus, graves ' disease, autoimmune myocarditis, membranous glomerulonephritis, diabetes mellitus, type I or type II diabetes mellitus, multiple sclerosis, raynaud's syndrome, autoimmune thyroiditis, gastritis, celiac disease, vitiligo, hepatitis, primary biliary cirrhosis, inflammatory bowel disease, spondyloarthropathies, experimental autoimmune encephalomyelitis, immune neutropenia, juvenile onset diabetes mellitus, immune responses associated with T lymphocyte mediated delayed hypersensitivity reactions common in tuberculosis, sarcoidosis and polymyositis, polyarteritis, cutaneous vasculitis, pemphigus, pemphigoid, lung nephritis, szechuan syndrome, systemic sclerosis, and sjogren's syndrome. Accordingly, in some embodiments, the present application provides a method of a disease and/or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to an individual an effective amount of a composition (e.g., a pharmaceutical composition) comprising an anti-FcRn antibody (e.g., a full length anti-FcRn antibody), such as any one of the anti-FcRn antibodies described herein (e.g., a full length anti-FcRn antibody), in some embodiments, the individual is a human.
In some embodiments, a method of modulating FcRn and IgG Fc interactions is provided, comprising contacting FcRn in a cell or subject with an anti-FcRn antibody or antigen binding fragment, or an effective amount of a composition (e.g., a pharmaceutical composition) comprising any one of the anti-FcRn antibodies (e.g., a full length anti-FcRn antibody). In some embodiments, the modulation inhibits the interaction between FcRn and IgG Fc. Thus, a method of promoting antibody degradation in a cell or individual is provided. In some embodiments, the antibody is an autoantibody. In some embodiments, the individual is a human.
In some embodiments, a method of treating or ameliorating an individual having an IgG-mediated disease is provided, comprising administering to the individual an anti-FcRn antibody or antigen binding fragment, or a composition (e.g., a pharmaceutical composition) comprising any one of the anti-FcRn antibodies (e.g., a full-length anti-FcRn antibody). The IgG-mediated diseases include pathogenic IgG antibody-related diseases including coagulopathy, vascular diseases, collagenosis, skin diseases, neuropathy, inflammatory bowel diseases, and organ-specific diseases. In some embodiments, the individual is a human.
In some embodiments, a method of blocking trans-placental transmission of pathogenic antibodies is provided, comprising administering to a pregnant mammal in need thereof a therapeutically effective amount of an anti-FcRn antibody or antigen binding fragment, or a composition (e.g., a pharmaceutical composition) comprising any one of the anti-FcRn antibodies (e.g., a full length anti-FcRn antibody).
In some embodiments, a method of inhibiting FcRn binding to an Immune Complex (IC) is provided, comprising contacting FcRn in a cell or individual with an anti-FcRn antibody or antigen binding fragment, or a composition (e.g., a pharmaceutical composition) comprising any one of the anti-FcRn antibodies (e.g., a full length anti-FcRn antibody). Thus, there is also provided a method of inhibiting Antigen Presenting Cells (APCs) from presenting an immune complex antigen, comprising contacting the APCs with an amount of an anti-FcRn antibody or antigen binding fragment, or a composition (e.g., a pharmaceutical composition) comprising any of the anti-FcRn antibodies (e.g., full length anti-FcRn antibodies). In some embodiments, the individual is a human.
In some embodiments, a method of increasing IC clearance in an individual is provided, comprising administering to an individual in need thereof an anti-FcRn antibody, an antigen binding fragment, or a composition (e.g., a pharmaceutical composition) comprising any one of the anti-FcRn antibodies (e.g., a full length anti-FcRn antibody). The methods are useful for treating IC-mediated vasculitis. In some embodiments, the individual is a human.
In some embodiments, a method of inhibiting secretion of an inflammatory cytokine by an Antigen Presenting Cell (APC) is provided, comprising contacting the APC with an anti-FcRn antibody, an antigen binding fragment, or a composition (e.g., a pharmaceutical composition) comprising any of the anti-FcRn antibodies (e.g., full length anti-FcRn antibodies). Inflammatory cytokines include, but are not limited to, interleukin-12 (IL-12), interleukin-6 (IL-6), and interferon gamma (IFNgamma).
In some embodiments, a method of inhibiting antigen presenting cells from activating T cells is provided, comprising contacting the antigen presenting cells with an anti-FcRn antibody, an antigen binding fragment, or a composition (e.g., a pharmaceutical composition) comprising any one of the anti-FcRn antibodies (e.g., a full length anti-FcRn antibody).
For example, in some embodiments, there is provided a method for treating an individual for a disease or disorder as described above (e.g., an autoimmune disease or inflammatory disease), comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-FcRn antibody (e.g., a full length anti-FcRn antibody), wherein the antibody comprises: heavy chain variable domain (V H ) The V is H Comprising: heavy chain complementarity determining region (HC-CDR) 1 comprising TYMN (SEQ ID NO: 1); HC-CDR2 comprising YIsX 1 X 2 SX 3 X 4 IYYADSVKG (SEQ ID NO: 44), wherein X 1 Is H or R, X 2 G, K, R or S, X 3 Is D or S, X 4 I, K or L; and HC-CDR3 comprising SWGX 1 X 2 GFDX 3 (SEQ ID NO: 45), wherein X 1 A, K, R of a shape of A, K, ROr V, X 2 A, I or V, X 3 I, L or V; light chain variable domains (V L ) The V is L Comprising: light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLX 1 X 2 X 3 X 4 GX 5 Nyld (SEQ ID NO: 46), wherein X 1 G, I, L or V, X 2 G, H, Q or Y, X 3 E, S or V, X 4 Is N or S, X 5 Is F or Y; LC-CDR2 comprising LGSNRAS (SEQ ID NO: 29); and LC-CDR3 comprising X 1 QX 2 X 3 X 4 X 5 PT (SEQ ID NO: 47), wherein X 1 Is L or M, X 2 A, S or Y, X 3 H, I, L or V, X 4 D, G, H, Q, R or S, X 5 S, T or V. In some embodiments, the anti-FcRn antibody is a full length antibody. In some embodiments, the full length anti-FcRn antibody is an IgG1 or IgG4 antibody. In some embodiments, the disease or condition is selected from, for example, myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, guillain-barre syndrome, lupus, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, rheumatoid arthritis, systemic lupus erythematosus, graves 'disease, autoimmune myocarditis, membranous glomerulonephritis, diabetes mellitus type I or type II diabetes, multiple sclerosis, raynaud's syndrome, autoimmune thyroiditis, gastritis, celiac disease, vitiligo, hepatitis, primary biliary cirrhosis, inflammatory bowel disease, spondyloarthropathies, experimental autoimmune encephalomyelitis, immune neutropenia, juvenile onset diabetes, immune responses associated with T-lymphocyte mediated delayed hypersensitivity reactions common in cytokines, tuberculosis, sarcoidosis and polymyositis, polyarteritis, cutaneous vasculitis, pemphigus-like, lung syndrome, kawasp, systemic sclerosis, szechuan of the like, and anti-inflammatory syndrome. In some embodiments, the individual is a human.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1, HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9, and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR comprising the amino acid sequence 1 as shown in any one of SEQ ID NOs 18-28, LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30-43, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising an amino acid sequence set forth in any one of SEQ ID NOs 48-61 or a variant thereof having at least about 80% sequence identity to an amino acid sequence set forth in any one of SEQ ID NOs 48-61; v (V) L The V is L Comprising an amino acid sequence as set forth in any one of SEQ ID NOs.62-82 or a variant thereof having at least about 80% sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs.62-82.
In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:2, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:30, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 48 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 48; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 62 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 62. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments The light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 49 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 49; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, a method for treating a disease is providedA method of an individual of a disease or disorder as described above (e.g., an autoimmune disease or inflammatory disease), comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:4, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:11, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 50 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 50; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of an antibody comprising an anti-FcRn antibodyWherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 64. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO 1, HC-CDR2Comprising the amino acid sequence SEQ ID NO. 3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO. 12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 20, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 33, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 65 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 65. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H Variants of (2) comprising in the HC-CDRsSubstitutions of up to about 5 amino acids; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 66. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2,comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 35, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 53 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 53; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 67. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:36, or said V L Variants of (2) comprising in the LC-CDRsSubstitutions of up to about 5 amino acids.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 54 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 54; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 68. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 23, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 54 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 54; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 69 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 69. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 38, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; to be used forV (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 70 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 70. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:13, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 39, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 55 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 55; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 71 or a variant thereof having at least about the amino acid sequence SEQ ID NO. 71 80% sequence identity. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:14, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 24, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 56 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 56; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 72. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, whatThe IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:15, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 25, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 35, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 57 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 57; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 73 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 73. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. At the position of In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:11, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 58 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 58; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 26, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 33, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 74 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 74. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some casesIn embodiments, there is provided a method for treating an individual having a disease or disorder as described above (e.g., an autoimmune disease or inflammatory disease), comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 75 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 75. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual with a disease or disorder as described above (e.g., an autoimmune disease or inflammatory disease), comprising administering to the individualAdministering in vivo an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:7, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 59 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 59; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 76 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 76. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1, packageComprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 41, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 77. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 42, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 78. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprisingAmino acid sequence SEQ ID NO 27, LC-CDR2 comprising amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising amino acid sequence SEQ ID NO 42, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 79. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 28, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 37, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 80 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 80. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:16, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 43, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an antibody described hereinThe FcRn antibody comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 60 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 60; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 81 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 81. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:14, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 56 or a variant thereof, said variant being identical to the amino acid sequence SEQ ID NO56 has at least about 80% sequence identity; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 82 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 82. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, there is provided a method for treating an individual having a disease or disorder (e.g., an autoimmune disease or inflammatory disease) as described above, comprising administering to the individual an effective amount of a composition comprising an anti-FcRn antibody, wherein the antibody comprises: v (V) H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:9, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:17, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34, or said V L Comprising up to about 5 amino acid substitutions in the LC-CDRs.
In some embodiments, an anti-FcRn antibody described herein comprises: v (V) H The V is H Comprising the amino acid sequence SEQ ID NO. 61 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 61; v (V) L The V is L Comprising the amino acid sequence SEQ ID NO. 66 or a variant thereof Has at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 66. In some embodiments, the anti-FcRn antibodies described herein are full length anti-FcRn antibodies comprising an IgG1 or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO. 86.
In some embodiments, the individual is a mammal (e.g., human, non-human primate, rat, mouse, cow, horse, pig, sheep, goat, dog, cat, etc.). In some embodiments, the individual is a human. In some embodiments, the individual is a clinical patient, a clinical trial volunteer, a laboratory animal, or the like. In some embodiments, the individual is less than 60 years old (including, for example, less than 50, 40, 30, 25, 20, 15, or 10 years old). In some embodiments, the individual is older than 60 years (including, for example, older than 70, 80, 90, or 100 years). In some embodiments, the individual is diagnosed with or genetically predisposed to one or more of the diseases or disorders described herein (e.g., autoimmune or inflammatory diseases). In some embodiments, the individual has one or more risk factors associated with one or more diseases or disorders described herein.
In some embodiments, the present application provides a method of delivering an anti-FcRn antibody (e.g., any one of the anti-FcRn antibodies described herein, e.g., an isolated anti-FcRn antibody) to a cell expressing FcRn on its surface in an individual, the method comprising administering to the individual a composition comprising the anti-FcRn antibody.
Many diagnostic methods for autoimmune or inflammatory diseases or any other disease that exhibits aberrant expression of FcRn and clinical descriptions of such diseases are known in the art. Such methods include, but are not limited to, for example, immunohistochemistry, PCR, and Fluorescence In Situ Hybridization (FISH).
In some embodiments, the anti-FcRn antibodies (e.g., full length anti-FcRn antibodies) and/or compositions described herein are used in combination with a second, third, or fourth agent (including, e.g., monoclonal antibody therapies for treating immune-mediated diseases, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, inhibitors of the complement system, immunosuppressives, immunomodulators, or combinations thereof) to treat diseases associated with the FcRn signaling pathway.
In some embodiments, a therapeutic effect refers to ameliorating or preventing a disease or disorder of interest, or exhibiting a detectable therapeutic or prophylactic effect. In some embodiments, the effect refers to reducing the level of circulating IgG. In some embodiments, the reduction in circulating IgG levels may be restored within 1 week or more after administration of the anti-FcRn antibody.
Dosage and method of administration of anti-FcRn antibodies
The dosage of an anti-FcRn antibody (e.g., isolated anti-FcRn antibody) composition administered to an individual (e.g., human) may vary with the particular composition, mode of administration, and type of disease being treated. In some embodiments, the amount of the composition (e.g., a composition comprising an anti-FcRn antibody) is effective to produce an objective response (e.g., a partial response or a complete response) in the treatment of an autoimmune disease or inflammatory disease. In some embodiments, the amount of the anti-FcRn antibody composition is sufficient to produce a complete response in the individual. In some embodiments, the amount of the anti-FcRn antibody composition is sufficient to produce a partial response in the individual. In some embodiments, the administered dose of the anti-FcRn antibody composition (e.g., when administered alone) is sufficient to produce a total response rate of greater than 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 64%, 65%, 70%, 75%, 80%, 85%, or 90% in a population of individuals treated with the anti-FcRn antibody composition. The response of an individual to the methods of treatment described herein can be determined, for example, by FcRn binding activity to IgG fc, circulating IgG levels, and/or half-life.
In some embodiments, the amount of the composition (e.g., a composition comprising an isolated anti-FcRn antibody) is sufficient to extend the progression-free survival of the individual. In some embodiments, the amount of the composition is sufficient to extend the overall survival of the individual. In some embodiments, the amount of the composition (e.g., when administered alone) is sufficient to produce a clinical benefit of greater than 50%, 60%, 70%, or 77% in a population of individuals treated with the anti-FcRn antibody composition.
In some embodiments, the amount of a composition (e.g., a composition comprising an isolated anti-FcRn antibody), alone or in combination with a second, third, and/or fourth agent, is sufficient to reduce FcRn binding activity to IgG Fc, reduce the half-life of circulating IgG, and/or reduce circulating IgG levels by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or 100% prior to treatment or as compared to the corresponding activity in other subjects not receiving treatment. The magnitude of the therapeutic effect can be measured using standard methods, such as in vitro assays for purified enzymes, cell-based assays, animal models, or human trials.
In some embodiments, the amount of anti-FcRn antibody (e.g., full length anti-FcRn antibody) in the composition is below a level that causes a toxic effect (i.e., an effect above a clinically acceptable toxicity level) or at a level where potential side effects can be controlled or tolerated when the composition is administered to an individual.
In some embodiments, the amount of the composition approaches the Maximum Tolerated Dose (MTD) of the composition following the same dosing regimen. In some embodiments, the amount of the composition is greater than 80%, 90%, 95% or 98% of the MTD.
In some embodiments, the amount of anti-FcRn antibody (e.g., full length anti-FcRn antibody) in the composition is in the range of 0.001 μg to 1000 μg.
In any of the embodiments described above, the effective amount of anti-FcRn antibody (e.g., full length anti-FcRn antibody) in the composition is in the range of 0.1 μg/kg to 100mg/kg as calculated at body weight.
The anti-FcRn antibody composition may be administered to a subject (e.g., a human) by a variety of routes including, for example, intravenous, intra-arterial, intraperitoneal, intrapulmonary, oral, inhalational, intravascular, intramuscular, intratracheal, subcutaneous, intraocular, intrathecal, mucosal or transdermal. In some embodiments, a slow release formulation of the composition is used. In some embodiments, the composition is administered intravenously. In some embodiments, the composition is administered through an artery. In some embodiments, the composition is administered intraperitoneally. In some embodiments, the composition is administered intrahepatially. In some embodiments, the composition is administered by hepatic arterial infusion. In some embodiments, the composition is applied to a site remote from the first lesion.
Product and kit
In some embodiments of the present application, an article of manufacture is provided, the article of manufacture comprising a substance that can be used to treat a disease or disorder as described above (e.g., an autoimmune disease or inflammatory disease), or to deliver an anti-FcRn antibody (e.g., a full length anti-FcRn antibody) to cells that surface express FcRn. The article of manufacture may comprise a container and a label or package insert attached to or associated with the container. Suitable containers include, for example, bottles, vials, syringes, and the like. The container may be made of a variety of materials, such as glass or plastic. Typically, the container contains a composition effective to treat the diseases or conditions described herein and has a sterile port (e.g., the container may be an iv bag or a vial with a pierceable cap of a hypodermic injection needle). At least one active substance in the composition is the anti-FcRn antibody described herein. The label or package insert identifies the particular condition for which the composition may be used. The label or package insert further comprises instructions for administering the anti-FcRn antibody composition to the patient. Articles of manufacture and kits comprising combination therapies are within the contemplation herein.
Package insert refers to instructions that are typically contained within the commercial package of therapeutic products, including indications, usage, dosage, administration, contraindications, and/or warning information regarding the use of such therapeutic products. In some embodiments, the package insert indicates that the composition may be used to treat a disease or disorder as described above (e.g., an autoimmune disease or an inflammatory disease). In some embodiments, the package insert indicates that the composition can be used to treat a disease including myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, guillain-barre syndrome, lupus, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, rheumatoid arthritis, systemic lupus erythematosus, graves 'disease, autoimmune myocarditis, membranous glomerulonephritis, diabetes mellitus type I or type II diabetes, multiple sclerosis, raynaud's syndrome, autoimmune thyroiditis, gastritis, celiac disease, vitiligo, hepatitis, primary biliary cirrhosis, inflammatory bowel disease, spondyloarthropathies, experimental autoimmune encephalomyelitis, immune neutropenia, juvenile onset diabetes, immune responses associated with T lymphocyte mediated hypersensitivity common in cytokines, tuberculosis, sarcoidosis and polymyositis, polyarteritis, cutaneous vasculitis, pemphigus, szeppy, szechuan syndrome, szechuan of the system, szechuan-case of the syndrome, szechuan-of the like, szechuan-type II syndrome.
In addition, the article of manufacture may further comprise a second container comprising a pharmaceutically acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate buffer, grignard solution, or dextrose solution. Other materials may be included as desired from a commercial and user standpoint, including other buffers, diluents, filters, needles and syringes.
Also, kits useful for various purposes, e.g., for treating a disease or disorder as described above (e.g., an autoimmune disease or inflammatory disease), or for delivering an anti-FcRn antibody (e.g., a full length anti-FcRn antibody) to cells that express FcRn on their surfaces, optionally in combination with a preparation. Kits of the present application comprise one or more containers comprising an anti-FcRn antibody composition (or single dose form and/or article of manufacture), and in some embodiments, further comprising another agent (e.g., an agent described herein) and/or instructions for use consistent with any of the methods described herein. The kit may further comprise a description of the selection of suitable individuals for treatment. The instructions for use attached to the kits herein are typically written instructions on labels or packaging instructions (e.g., paper sheets contained within the kits), and machine-readable instructions (e.g., instructions on magnetic or optical storage discs) are also acceptable.
For example, in some embodiments, the kit comprises a composition comprising an anti-FcRn antibody (e.g., a full length anti-FcRn antibody). In some embodiments, the kit comprises: a) A composition comprising any one of the anti-FcRn antibodies described herein, and b) at least one additional agent in an amount effective to enhance the effect (e.g., therapeutic effect, detection effect) of the anti-FcRn antibody. In some embodiments, the kit comprises: a) A composition comprising any one of the anti-FcRn antibodies described herein, and b) instructions for administering the anti-FcRn antibody composition to an individual for use in treating a disease associated with an FcRn signaling pathway (e.g., an autoimmune disease or an inflammatory disease). In some embodiments, the kit comprises: a) a composition comprising any one of the anti-FcRn antibodies described herein, and b) at least one additional agent in an amount effective to enhance the effect (e.g., therapeutic effect, detection effect) of the anti-FcRn antibody and c) instructions for administering the anti-FcRn antibody composition and additional agent to an individual for use in treating a disease or disorder (e.g., autoimmune disease or inflammatory disease) as described above. The anti-FcRn antibody and other substances may be present in separate containers or in the same container. For example, the kit may comprise one specific composition or two or more compositions, wherein one composition comprises an anti-FcRn antibody and the other composition comprises another agent.
In some embodiments, the kit comprises a nucleic acid (or a set of nucleic acids) encoding an anti-FcRn antibody (e.g., a full length anti-FcRn antibody). In some embodiments, the kit comprises: a) A nucleic acid (or a set of nucleic acids) encoding an anti-FcRn antibody (e.g., a full length anti-FcRn antibody), and b) a host cell expressing the nucleic acid (or the set of nucleic acids). In some embodiments, the kit comprises: a) A nucleic acid (or set of nucleic acids) encoding an anti-FcRn antibody (e.g. a full length anti-FcRn antibody), and b) instructions for use, adapted to: i) Expressing an anti-FcRn antibody in a host cell, ii) preparing a composition comprising the anti-FcRn antibody, and iii) administering the composition comprising the anti-FcRn antibody to an individual to treat a disease or disorder as described above (e.g., an autoimmune disease or inflammatory disease). In some embodiments, the kit comprises: a) a nucleic acid (or set of nucleic acids) encoding an anti-FcRn antibody (e.g., a full length anti-FcRn antibody), b) a host cell expressing the nucleic acid (or set of nucleic acids), and c) instructions for use, suitable for: i) Expressing an anti-FcRn antibody in a host cell, ii) preparing a composition comprising the anti-FcRn antibody, and iii) administering the composition comprising the anti-FcRn antibody to an individual to treat a disease or disorder as described above (e.g., an autoimmune disease or inflammatory disease).
The kits described herein are packaged in a suitable form. Suitable packages include, but are not limited to, vials, bottles, jars, flexible packages (e.g., sealed mylar or plastic bags), and the like. The kit may optionally provide additional components, such as buffers and instructional information. Thus, the present application also provides articles, including vials, bottles, jars, flexible packages (e.g., sealed mylar or plastic bags), and the like.
Instructions for use of the anti-FcRn antibody compositions typically include information such as, for example, dosage, period of administration, route of administration, and the like. The container may be unit dose, large package (e.g., multi-dose package) or subunit dose. For example, a kit comprising a sufficient dose of an anti-FcRn antibody as described herein (e.g., a full length anti-FcRn antibody) is provided for long-term effective treatment of an individual, e.g., one week, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 7 months, 8 months, 9 months, or more. The kit may further comprise multiple unit doses of the anti-FcRn antibody, pharmaceutical compositions, and instructions for use, and be packaged in amounts sufficient for storage and use in a pharmacy, e.g., a hospital pharmacy and a compounding pharmacy.
Those skilled in the art will recognize several embodiments that are possible within the scope and spirit of the present application. The present application will now be described in more detail by reference to the following non-limiting examples. The following examples further illustrate the present application but should not be construed as in any way limiting its scope.
Detailed Description
In the examples disclosed below, the following abbreviations apply: fcRn (Neonatal Fc receptor ); hFCGRT (human FCGRT, human FcRn-alpha); hB2M (human β2-microglobulin); cyFcRn (cynomolgus FcRn-alpha); mFcRn (mouse FcRn-alpha); rFcRn (rat FcRn-alpha); bavih-hFCGRT (Biotin-hFCGRT-Avi-10 His)
Example 1: preparation of recombinant FcRn antigen and screening for single chain antibodies (scFv) against FcRn
Preparation of recombinant FcRn antigen
FcRn is a non-covalent heterodimer consisting of an alpha chain (FCGRT) and beta 2-microglobulin (B2M). The coding sequences of codon optimized hFCGRT (np_ 001129491.1), hB2M (np_ 004039.1), cyFcRn (np_ 001271480.1), mFcRn (np_ 001344046.1) and rFcRn (np_ 203502.1) were synthesized separately and fused with His-tag and constructed into mammalian cell expression vector pTTa1, respectively constructing the following expression vectors: pTTa1-hFCGRT-10His, pTTa1-hFCGRT-Avi-10His, pTTa1-hB2M-10His, pTTa1-cyFcRn-10His, pTTa1-mFcRn-10His, pTTa1-rFcRn-10His. Where "His or His" stands for His tag and "Avi" stands for avidin tag.
The recombinant FcRn described above was expressed and purified according to the manufacturer's instructions. Briefly, 293F cells were transfected with the expression vectors, respectively, and the cells were subjected to 8% CO at 37 ℃ 2 Culturing for 5 days at 120 rpm. For purification of His-tag protein, cell culture solution was collected, the supernatant was loaded into a Hisnap column, equilibrated with 20mM sodium phosphate buffer (pH 7.4) containing 0.25M NaCl and 5mM imidazole (pH 8.0), the column was washed with 20mM sodium phosphate buffer (pH 7.4) containing 0.25M NaCl and 15mM imidazole (pH 8.0), and then eluted with 20mM sodium phosphate buffer (pH 7.4) containing 0.25M NaCl and 100mM imidazole (pH 8.0).
Preparation of biotinylated-tagged hFCGRT antigen
The hFCGRT-Avi-10His was biotinylated using the biotinylated ligase B0101A (GeneCopoeia) according to the protocol. Briefly, buffer A/B and BirA ligase were added to the hFCGRT-Avi-10His antigen and incubated at 30℃for 2 hours. Biotinylated FCGRT (i.e., biotin-hFCGRT-Avi-10 His) was designated as Bavih-hFCGRT. The biotinylation efficiency was measured by ELISA method. Briefly, the initial concentration of Bavih-hFCGRT was set at 500ng/ml, at 1:2, and coating ELISA plates after dilution. SA-HRP was used for detection and biotinylated standards were used as controls. The biotinylation labeling efficiency of Bavih-hFCGRT is 70%.
Screening for anti-FcRn Single chain antibodies (scFv)
Construction of scFv antibody yeast display library: RNA is extracted from 2000 human blood samples, cDNA is obtained through reverse transcription, and V is adopted H And V K Specific primer amplification V H And V K Fragment, after gel recovery and purification, is connected with V H And V K The scFv was constructed and cloned into the yeast display plasmid PYD1, which was then electrotransferred into yeast to obtain a scFv antibody yeast display library.
Screening for anti-FcRn single chain antibodies (scFv): scFvs recognizing hFCGRT were isolated from the yeast display library. Briefly, yeast cells expressing scFv were enriched using MACS magnetic bead sorting. 1000OD yeast cells were centrifuged at 2500g for 5 min. The cell pellet obtained was resuspended in 1L SGCAA medium at an initial concentration of od600=1 and induced to express at 20 ℃ under culture conditions of 250rpm for 40-48 hours. After centrifugation of the cell culture and washing with PBSM solution, the cell pellet was resuspended in 5-10 volumes of PBSM solution containing 1. Mu.M Bavih-hFCGRT and incubated for 1 hour at 4 ℃. After centrifugation and PBSM washing, unbound antigen is washed away by PBSM solution. After the addition of the beads, they were thoroughly mixed and then incubated on a suspension rotator at 4℃for 30 minutes. 2500g centrifugal 5 minutes, discard supernatant, with 5-10 times the volume of PBSM solution heavy suspension precipitation. 7ml of cell suspension was added to the column each time until all of the cell suspension flowed through the column. The cells bound to the column were collected and further cultured to extract plasmids.
Phage display libraries were prepared and scFv antibodies were screened: PC of plasmids obtained from Yeast pool Using scFv-F and scFv-R primersR amplification, cloning the obtained scFvs antibody fragment into a phage display vector pDAN5 through SfiI, and transforming TG1 phage display electroporation competent cells after connection to obtain an scFv antibody phage display library. scFv antibodies that specifically bind hFCGRT were isolated from phage display libraries through a series of repeated screening steps. Briefly, take 2X 10 11 The phage scFv library of PFU was added to Bavih-hFCGRT and incubated at 37℃for 2 hours. Phage that bound to Bavih-hFCGRT were captured by streptavidin-coated magnetic beads, while unbound phage were washed away. After washing with TBST solution for 8-15 times (washing times increased with increasing number of screening rounds), phages specifically binding to hFCGRT were eluted with Glycine-HCl solution (pH 2.2). These phages were used to infect TG1 cells in exponential growth phase, and after ampicillin addition for 1 hour, helper phages were added and shake cultured overnight at 28℃at 200 rpm. The culture solution is collected the next day, supernatant is obtained after centrifugation, and the next round of screening is carried out until a positive scFv antibody library is obtained.
scFv single chain antibodies were screened using ELISA binding assays. ELISA binding assays were performed on phages enriched after MACS panning to screen scFv single chain antibodies. Briefly, human hFCGRT antigen was dissolved in PBS solution and coated in 96-well plates at 0.1 μg/well overnight at 4 ℃. Prior to antibody addition, 96-well plates were washed with PBST solution. mu.L of PBS containing 4% nonfat milk powder was added to each well, followed by 10. Mu.L of scFv-expressing phage supernatant to the corresponding well, and incubated at 37℃for 1-2 hours. After washing with PBST solution, HRP-labeled anti-M13 mab (1:4000 dilution, vendor Sino Biological, cat# 11973-MM 05T-H) was added and incubated at 37℃for 1H at 100. Mu.L/well. PBST plates were washed 3 times, TMB chromogenic solution was added, 100. Mu.L/well, and incubated at room temperature for 10min in the dark. By 2M H 2 SO 4 The chromogenic reaction was terminated and the absorbance at 450nm was read with a microplate reader. And selecting positive clone bacteria for sequencing, and extracting phage display plasmids for later use after amplifying and culturing the positive clone bacteria with correct sequencing. After the screening process was completed, a series of positive scFv antibodies were obtained.
scFv single chain antibodies were screened using IgG blocking experiments: screening by IgG blocking experimentsA positive scFv antibody having an activity of inhibiting IgG binding to FcRn. Briefly, commercial hIgG (Jackson ImmunoResearch, 009-000-003) was coated onto 96-well ELISA plates (Corning, 9018) overnight at 4 ℃. Then blocked with 1% BSA, incubated at room temperature for 1 hour to block non-specific binding. After washing the plates, bavih-hFCGRT and scFv samples were added sequentially, reacted at 37℃for 1 hour, then HRP-labeled streptavidin (ABCAM, cat#AB 7403) was added, reacted at 37℃for 1 hour, the plates were washed, incubated with 50. Mu.L/well TMB for 5-10min, and 2MH was added 2 SO 4 The color development was terminated and the microplate reader read OD450.
Example 2: preparation and characterization of full-length human anti-FcRn antibodies
Preparation of full-length anti-FcRn antibodies
The most potential scFv antibodies were constructed as human IgG1 or IgG4 antibody molecules with a heavy chain constant region of human IgG1 or IgG4 and a human kappa or lambda light chain constant region. Amplification of V L And V H Into eukaryotic expression vectors pTT5-K (comprising kappa constant regions) or pTT5-L (comprising lambda constant regions), and pTT5-H1 (comprising IgG1 heavy chain constant regions) or pTT5-H4 (comprising IgG4 heavy chain constant regions), respectively. Respectively extracting plasmids expressing light/heavy chains, co-transfecting 293F cells, and performing 8% CO at 37 DEG C 2 Culturing at 120rpm for 5 days, and purifying the culture solution by using a protein A affinity chromatography column. Briefly, the protein A column was first equilibrated with 6 column volumes of 50mM PBS buffer (pH 7.2) containing 0.15M NaCl at a flow rate of 150 cm/h. The culture supernatant (pH adjusted to 7.2) was passed through the column at a flow rate of 150 cm/h. After further equilibration, the eluate was collected by elution with 50mM citric acid-sodium citrate buffer (pH 3.5). Of the full-length antibodies constructed, F01 was selected as the lead antibody.
Fab yeast display libraries containing CDR region mutations were prepared with F01 Fab. The biological activity of antibody variants that bind to hFcRn with high affinity was evaluated. Fab antibodies with increased hFcRn binding activity compared to F01 Fab were selected to construct full length antibodies. A new round of screening was performed on full-length antibodies. The selected optimized antibodies are then subjected to further biochemical and biological analysis.
Briefly, to the pilotThe antibody F01 molecule undergoes affinity maturation. First, construction of 2 yeast display libraries was completed for the lead antibody F01, namely L1L3H2H3 antibody libraries (stock capacity 3X 10 8 ) And L3H3 antibody library (stock capacity of 2X 10) 7 ). Yeast display library preparation procedure was as described above. The 2 antibody pools were then mixed and then sorted using FACS, and the positive antibody population that strongly bound to hFCGRT antigen was sorted under ph6.0 binding conditions. Extracting positive yeast group plasmids, constructing the positive yeast group plasmids on an IgG secretion expression vector, extracting plasmids, transfecting 293 cells, performing ELISA binding detection on cell supernatants, and picking positive hole plasmids which are strongly bound with hFCGRT antigen to obtain a series of optimized antibodies (F02-F24).
Affinity of anti-FcRn antibodies
The affinity of the lead antibody F01 and the optimized antibody (reconstituted as human IgG 4) for hFcRn was evaluated using ELISA experiments. Briefly, 1. Mu.g/mL of hFcRn antigen (human FCGRT&B2M heterodimeric recombinant protein, sino biological, cat#ct 009-H08H) was coated with 96-well elisa plate, overnight at 4 ℃. The coating solution was removed, blocking buffer containing 1% bsa was added and incubated for 1 hour at room temperature. Plates were washed 3 times, and gradient diluted antibodies were added and reacted at 37℃for 1 hour. Plates were washed 3 times, 50. Mu.L/well HRP-labeled goat anti-human IgG Fab secondary antibody (1:3000 dilution, jackson ImmunoResearch cat # 109-036-097) was added and reacted at 37℃for 1 hour. Wash with wash buffer 5 times. Then 50. Mu.L/well TMB was added for 5-10min at room temperature, and after the completion of the color development, 2M sulfuric acid was added to terminate the reaction. OD450 was read and binding curves were generated by PRISM to calculate EC 50 Values.
The results are shown in table 5, all optimized antibodies (reconstituted to human IgG 4) exhibited higher or comparable hFcRn binding affinities compared to the lead antibody F01.
TABLE 5
Antibodies to EC 50 (nM) Antibodies to EC 50 (nM)
F01 2.55 F13 0.34
F02 1.11 F14 0.15
F03 0.69 F15 2.61
F04 0.99 F17 0.21
F05 0.82 F18 1.21
F06 0.93 F19 0.93
F07 0.29 F20 1.09
F08 0.27 F21 1.00
F09 0.61 F22 0.27
F10 0.37 F23 0.29
F11 0.11 F24 0.37
F12 0.15
Example 3: binding inhibition activity assay for anti-FcRn antibodies
The inhibitory activity of the lead antibody F01 and the optimized antibody (reconstituted as human IgG 4) on IgG binding to FcRn was detected by ELISA. Briefly, commercial hIgG (Jackson ImmunoResearch, 009-000-003) was coated onto 96-well ELISA plates at 4℃overnight. Blocking for 1 hour at room temperature by adopting 1% BSA, washing the plate, adding the Bavih-hFCGRT and the antibody subjected to gradient dilution, and reacting for 1 hour at 37 ℃. After that, 100. Mu.L/well HRP-labeled streptavidin (1:20000) was added thereto and reacted at 37℃for 1 hour. After washing the plate, 50. Mu.L/well TMB was added and developed at room temperature for 5-10min, followed byThe color development was stopped by adding 2M sulfuric acid. OD450 was read and binding curves were generated by PRISM to calculate IC 50 Values.
The results are shown in table 6, where the lead antibody F01 and the optimized antibody (reconstituted as human IgG 4) were able to block IgG binding to human FcRn, and the inhibitory activity on IgG binding to FcRn in vitro was significantly better than the control antibody Rozanolixizumab (UCB, anti-FcRn antibody).
TABLE 6
Antibodies to IC 50 (nM) Antibodies to IC 50 (nM)
F01 6.29 F14 6.68
F02 6.67 F15 2.83
F03 4.45 F16 3.30
F04 4.27 F17 4.92
F05 3.71 F18 3.81
F06 4.15 F19 3.42
F07 4.85 F20 4.05
F08 2.35 F21 3.25
F09 2.08 F22 3.67
F10 2.90 F23 7.34
F11 5.12 F24 1.75
F12 5.39 Rozanolixizumab 8.74
F13 2.58
Example 4: cyclic inhibition activity assay for anti-FcRn antibodies
FcRn has the property of pH-dependent binding to IgG antibodies and is a key receptor for maintenance of IgG-type immunoglobulin metabolism levels in vivo. MDCK cells are model cells that study FcRn transport of IgG. MDCK cells stably transfected with two subunits of human FcRn (hFCGRT and hB 2M) are capable of transporting human IgG, while anti-FcRn antibodies can block this activity, and the level of anti-FcRn antibody inhibitory activity is assessed by determining IgG concentration.
Co-transfection of two plasmids, pCMV3-hFCGRT-GFP and pCMV3-hB2M, into MDCK (ATCC, CCL-34) TM ) Cells, monoclonal cell line MDCK-4#, which stably expressed hFCGRT and hB2M subunits, were selected and thus were able to circulate human IgG. MDCK-4# cells were seeded in 96-well plates and after the cells reached the polarity requirement, the complete cell culture broth was removed and washed with HBSS buffer (pH 7.4) containing 1% BSA. Thereafter, 100. Mu.L of HBSS buffer (pH 7.4) containing 1% BSA was added to each well, and the mixture was pre-equilibrated in an incubator for 20 minutes. Adding diluted anti-FcRn antibody, standing at 37deg.C and 5% CO 2 Incubation in a conditioned incubator for 1 hour. Removing antibody dilution, washing with 100 μl of HBSS buffer (pH 5.9) containing 1% BSA per well, adding prepared biotinylated IgG (Jackson ImmunoResearch, 009-060-003) to cell plate, standing at 37deg.C, 5% CO 2 Incubation in a conditioned incubator for 1 hour. Wash with HBSS buffer (pH 5.9). Then 100. Mu.L of HBSS buffer (pH 7.4) was added to each well and the mixture was left to stand at 37℃with 5% CO 2 Incubation in a conditioned incubator for 2 hours. Cell supernatants were collected for ELISA experiments.
Commercial goat anti-human IgG Fc antibody (Southern Biotec)h, 2014-01) coating the ELISA plate, and incubating at 4 ℃ overnight. Blocking with 1% BSA, blocking at room temperature for 1 hr, washing, adding 55 μl of MDCK cell supernatant, reacting at 37deg.C for 1.5 hr, adding HRP-labeled streptavidin, reacting at 37deg.C for 1 hr, developing color with TMB at room temperature, adding 2M sulfuric acid to terminate color development, reading OD450, generating binding curve by PRISM, and calculating IC 50 Values.
The results are shown in table 7, the lead antibody and the optimized antibody can inhibit the circulation of human IgG, and the circulation inhibition activity on IgG is equivalent to that of the positive control antibody rozanolizumab (UCB, anti-FcRn antibody), even superior to that of the control antibody.
TABLE 7
Antibodies to IC 50 (nM) Antibodies to IC 50 (nM)
F01 9.526 F10 3.56
F02 11.46 F11 11.78
F03 14.78 F12 7.28
F04 8.60 F13 2.42
F05 9.035 F14 2.77
F06 16.63 F15 12.87
F07 8.86 F16 16.59
F08 1.73 Rozanolixizumab 12.89
F09 1.53
EXAMPLE 5 binding specificity of anti-FcRn antibodies to the different subunits of hFcRn FCGRT and B2M
ELISA was used to detect the binding specificity of anti-FcRn antibodies to the different subunits of hFcRn FCGRT and B2M. Briefly, hFCGRT and hB2M antigens were individually coated onto 96-well ELISA plates, and incubated at room temperature for 1 hour after blocking with 1% BSA overnight at 4 ℃ When (1). After plate washing, gradient diluted anti-FcRn antibodies F02, F03, F14, F09 or F18 were added, respectively, and reacted at 37 ℃ for 1 hour. In FCGRT binding experiments, rozanoliximab (UCB, anti-FcRn antibody) was a positive control antibody and FY38 (an antibody that does not bind FcRn, derived from sulteus) was a negative control antibody; in the B2M binding experiment, anti-B2M (Sinobiological, cat#11976-MM 35) was used as a positive control antibody, and Rozanoliximab (UCB, anti-FcRn antibody) was used as a negative control antibody. After repeating the washing process, HRP-labeled goat anti-human IgG Fab secondary antibody was added, reacted at 37 ℃ for 1 hour, then developed with TMB at room temperature, and after the development was completed, the reaction was terminated by adding 2M sulfuric acid. OD450 was read and binding curves were generated by PRISM to calculate EC 50 Values.
The results show that anti-FcRn antibodies F02, F03, F14, F09, F18 and the positive control antibody Rozanolixizumab (UCB, anti-FcRn antibody) bound to the FCGRT subunit of human FcRn (fig. 1A) and none bound to the B2M subunit (fig. 1B).
Example 6 detection of Cross-binding Activity of anti-FcRn antibodies to FcRn of different species
The cross-binding activity of anti-FcRn antibodies to FcRn of different species including cynomolgus monkey, mouse and rat was examined by ELISA. Briefly, cyFcRn, mFcRn or rFcRn antigen was coated separately on 96-well elisa plates, overnight at 4 ℃, then blocked with 1% bsa, after plate washing, the gradient diluted anti-FcRn antibodies F02, F03, F14, F09, F18 and control antibodies were added separately, wherein in the cyFcRn binding assay, rozanolixizumab (UCB, anti-FcRn antibody) was the positive control antibody and FY38 was the negative control antibody (antibody that did not bind FcRn, derived from sultaishen); in the rFcRn binding and mFcRn binding experiments, M281 (Johnson &Johnson, anti-FcRn antibody) as a positive control antibody and rozanoliximab (UCB, anti-FcRn antibody) as a negative control antibody. After repeating the washing process, the HRP-labeled goat anti-human IgG Fab was added and reacted at 37℃for 1 hour, followed by color development at room temperature using TMB, and after the color development was completed, the reaction was terminated by adding 2M sulfuric acid. OD450 was read and binding curves were generated by PRISM to calculate EC 50 Values.
The results showed that anti-hFcRn antibodies F02, F03, F14, F09, and F18 cross-reacted with cynomolgus cyFcRn (fig. 2A), with weaker binding to rat rpcrn (fig. 2B), mouse mFcRn (fig. 2C).
Example 7 characterization of binding affinity and dissociation constant (Kd) of anti-FcRn antibodies
The binding affinity of anti-FcRn antibodies (reconstituted human IgG 4) was characterized using Biacore T200 (GE). The full-length anti-FcRn antibody was immobilized on the sensor chip CM 5. Affinity was measured for different concentrations of hFCGRT. Concentration ranges include 10, 5, 2.5, 1.25, 0.625, 0.3125, 0.15625, 0.078, 0.039, 0.0195 and 0nM, with 0.625 and 0nM repeated once, respectively. Binding and dissociation rates were measured using SPR techniques and binding affinities were determined.
The results are shown in table 8, where anti-FcRn antibodies F02, F03, F14, F18 were comparable to the control antibody rozanoliximab (UCB, anti-FcRn antibody).
TABLE 8
Antibodies to Kon(1/Ms) Koff(1/s) Kd(M)
F02 2.13E+7 4.67E-5 2.20E-12
F03 1.70E+7 2.70E-4 1.59E-11
F14 2.09E+7 4.71E-5 2.25E-12
F18 1.98E+7 4.86E-5 2.45E-12
Rozanolixizumab 8.39E+6 3.31E-5 3.94E-12
Example 8: effect of anti-FcRn antibodies on HSA content in cynomolgus monkeys
FcRn not only binds IgG, but also serum albumin (HSA), and the inhibition of HSA binding to FcRn by anti-FcRn antibodies was tested using the bromocresol green method. Briefly, cynomolgus monkeys were respectively intravenously injected with 10mg/kg of control antibody rozanolizumab (UCB, anti-FcRn antibody) and antibody to be tested, and blood samples were collected for each animal at 0h, 4h, 8h, 24h, 32h, 48h, 72h, 96h, 120h, respectively, after the injection of the antibody. After centrifugation, the plasma was analyzed for HSA content using bromocresol green.
The results are shown in fig. 3, where none of the anti-FcRn antibodies F02, F03, F14, F09, F18 and the control antibody rozanolizumab (UCB, anti-FcRn antibody) had a significant effect on the in vivo content of HSA, indicating that the anti-FcRn antibodies had no inhibitory activity on HSA binding to FcRn.
Example 9: pharmacodynamic studies of anti-FcRn antibodies in mice
In vivo studies were performed using mice transgenic for hFcRn expression to determine the effect of anti-FcRn antibodies on human IgG clearance. The experiment was performed with 6 healthy adult transgenic mice (C57 BL/6-Fcgrt tm1(hFcgrt) /Bcgen,BeijingBiocytogen Co.,Ltd) as a group. On day 0, all mice were pre-intravenously injected with hIgG at a concentration of 500mg/kg. After 24 hours of hIgG injection, mice were injected with anti-FcRn antibodies F02, F03, F14, F09 or F18 (reconstituted as human IgG 4) at a concentration of 30mg/kg. Rozanoliximab served as positive control and PBS buffer served as negative control. Blood samples were collected for each animal at 0h (i.e., 24 hours after the administration of hIgG and before the administration of anti-FcRn antibodies), 0.25h, 24h, 48h, 72h, 96h, 144h and 196h after the administration of antibodies. After centrifugation, plasma was analyzed for hIgG concentration by ELISA. The plasma concentration of mice at 0h (i.e. 24 hours after the injection of hIgG and before the injection of anti-FcRn antibody) was defined as 1.0, and the fold change in hIgG concentration relative to 0h was calculated from the plasma IgG concentrations at different time points.
As shown in fig. 4, the anti-FcRn antibody molecules F02, F03, F14, F09 and F18 were able to rapidly reduce IgG levels in mice compared to the negative control PBS, and all were better active than the control antibody Rozanolixizumab.

Claims (22)

  1. An isolated anti-FcRn antibody, wherein the anti-FcRn antibody comprises:
    heavy chain variable domain (V H ) The V is H Comprising:
    heavy chain complementarity determining region (HC-CDR) 1 comprising TYMN (SEQ ID NO: 1);
    HC-CDR2 comprising YIsX 1 X 2 SX 3 X 4 IYYADSVKG (SEQ ID NO: 44), wherein X 1 Is H or R, X 2 G, K, R or S, X 3 Is D or S, X 4 I, K or L; and
    HC-CDR3 comprising SWGX 1 X 2 GFDX 3 (SEQ ID NO: 45), wherein X 1 A, K, R or V, X 2 A, I or V, X 3 I, L or V; and
    light chain variable domain (V L ) The V is L Comprising:
    light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLX 1 X 2 X 3 X 4 GX 5 Nyld (SEQ ID NO: 46), wherein X 1 G, I, L or V, X 2 G, H, Q or Y, X 3 E, S or V, X 4 Is N or S, X 5 Is F or Y;
    LC-CDR2 comprising LGSNRAS (SEQ ID NO: 29); and
    LC-CDR3 comprising X 1 QX 2 X 3 X 4 X 5 PT (SEQ ID NO: 47), wherein X 1 Is L or M, X 2 A, S or Y, X 3 H, I, L or V, X 4 D, G, H, Q, R or S, X 5 S, T or V.
  2. An isolated anti-FcRn antibody comprising V H ，
    The V is H Comprising:
    HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO. 1 or a variant thereof comprising up to about 3 amino acid substitutions;
    HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs 2-9 or a variant thereof, said variant comprising up to about 3 amino acid substitutions; and
    HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 10-17 or a variant thereof, said variant comprising up to about 3 amino acid substitutions; and
    V L the V is L Comprising:
    LC-CDR1 comprising the amino acid sequence set forth in any one of SEQ ID NOs 18-28 or a variant thereof comprising up to about 3 amino acid substitutions;
    LC-CDR2 comprising the amino acid sequence shown in SEQ ID No. 29 or a variant thereof comprising substitutions of up to about 3 amino acids; and
    LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs 30 to 43 or a variant thereof comprising up to about 3 amino acid substitutions.
  3. An isolated anti-FcRn antibody comprising V H The V is H Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs 48-61 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3, and V L The V is L Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs 62-82 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
  4. An isolated anti-FcRn antibody according to claim 3, comprising:
    (i)V H comprising V as shown in amino acid sequence SEQ ID NO 48 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in the amino acid sequence SEQ ID NO. 62 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (ii)V H comprising V as shown in amino acid sequence SEQ ID NO. 49 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 63 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (iii)V H comprising V as shown in amino acid sequence SEQ ID NO 50 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 63 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (iv)V H comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 64 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (v)V H comprising V as shown in amino acid sequence SEQ ID NO:52 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 65 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (vi)V H comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:66 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (vii)V H comprising V as shown in amino acid sequence SEQ ID NO 53 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:67 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (viii)V H comprising V as shown in amino acid sequence SEQ ID NO:54 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 68 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (ix)V H comprising V as shown in amino acid sequence SEQ ID NO:54 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:69 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (x)V H comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in the amino acid sequence SEQ ID NO 70 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xi)V H comprising V as shown in amino acid sequence SEQ ID NO:55 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising, for example, amino groupsV shown in acid sequence SEQ ID NO 71 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xii)V H comprising V as shown in amino acid sequence SEQ ID NO:56 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:72 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xiii)V H comprising V as shown in amino acid sequence SEQ ID NO:57 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:73 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xiv)V H comprising V as shown in amino acid sequence SEQ ID NO 58 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 63 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xv)V H comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:74 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xvi)V H comprising V as shown in amino acid sequence SEQ ID NO:52 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO 75 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xvii)V H comprising V as shown in amino acid sequence SEQ ID NO 59 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO 76 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xviii)V H comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:77 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xix)V H comprising V as shown in amino acid sequence SEQ ID NO:52 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:78 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xx)V H comprising V as shown in amino acid sequence SEQ ID NO:52 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO:79 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xxi)V H comprising V as shown in amino acid sequence SEQ ID NO:51 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in the amino acid sequence SEQ ID NO 80 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xxii)V H comprising V as shown in amino acid sequence SEQ ID NO:60 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 81 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3;
    (xxiii)V H comprising V as shown in amino acid sequence SEQ ID NO:56 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising V as shown in amino acid sequence SEQ ID NO. 82 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3; or (b)
    (xxiv)V H Comprising V as shown in amino acid sequence SEQ ID NO. 61 H Comprising HC-CDR1, HC-CDR2 and HC-CDR3; v (V) L Comprising, for exampleV shown in amino acid sequence SEQ ID NO. 66 L Comprising LC-CDR1, LC-CDR2 and LC-CDR3.
  5. The isolated anti-FcRn antibody of any one of claims 1-4, wherein the anti-FcRn antibody binds to human FcRn with a Kd value of 0.1pM to 1nM.
  6. The isolated anti-FcRn antibody of any one of claims 1-5, comprising:
    (i)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:2, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:30, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (ii)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (iii)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:4, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:11, or the V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (iv)V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (v)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 20, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 33, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (vi)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H Variants of (C) HC-CSubstitutions comprising up to about 5 amino acids in DRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (vii)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 35, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (viii)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:18, LC-CDR2 comprising the amino acid sequence SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:36, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (ix)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; andV L the V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 23, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (x)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 38, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xi)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:13, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 39, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xii)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:14, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 24, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xiii)V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:15, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 25, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 35, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xiv)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:11, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 31, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xv)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 26LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 33, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xvi)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 32, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xvii)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:7, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 37, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xviii)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29,and LC-CDR3 comprising the amino acid sequence SEQ ID NO 41, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xix)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 19, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 42, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xx)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:12, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 27, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 42, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xxi)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:10, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO 28, LC-CDR2 comprising the amino acid sequence SEQ ID NO 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO 37,or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xxii)V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:16, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 22, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 43, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs;
    (xxiii)V H the V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:14, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 40, or said V L A variant of (2) comprising up to about 5 amino acid substitutions in the LC-CDRs; or (b)
    (xxiv)V H The V is H Comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:9, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:17, or said V H A variant of (2) comprising up to about 5 amino acid substitutions in the HC-CDRs; v (V) L The V is L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO. 21, LC-CDR2 comprising the amino acid sequence SEQ ID NO. 29, and LC-CDR3 comprising the amino acid sequence SEQ ID NO. 34, or said V L In a variant of (a) the above,the LC-CDRs of which comprise up to about 5 amino acid substitutions.
  7. The isolated anti-FcRn antibody of any one of claims 1-6, comprising:
    V H comprising an amino acid sequence set forth in any one of SEQ ID NOs 48-61 or a variant thereof having at least about 80% sequence identity to an amino acid sequence set forth in any one of SEQ ID NOs 48-61; v (V) L Comprising the amino acid sequence set forth in any one of SEQ ID NOs.62-82 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs.62-82.
  8. An isolated anti-FcRn antibody according to claim 7 comprising:
    (i)V H comprising the amino acid sequence SEQ ID NO. 48 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 48; v (V) L Comprising the amino acid sequence SEQ ID NO. 62 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 62;
    (ii)V H comprising the amino acid sequence SEQ ID NO. 49 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 49; v (V) L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63;
    (iii)V H comprising the amino acid sequence SEQ ID NO. 50 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 50; v (V) L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63;
    (iv)V H comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof, said variant being identical to the amino acid sequence SEQID NO. 51 has at least about 80% sequence identity; v (V) L Comprising the amino acid sequence SEQ ID NO. 64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 64;
    (v)V H comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 65 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 65;
    (vi)V H comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 66;
    (vii)V H comprising the amino acid sequence SEQ ID NO. 53 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 53; v (V) L Comprising the amino acid sequence SEQ ID NO. 67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 67;
    (viii)V H comprising the amino acid sequence SEQ ID NO. 54 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 54; v (V) L Comprising the amino acid sequence SEQ ID NO. 68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 68;
    (ix)V H comprising the amino acid sequence SEQ ID NO. 54 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 54; v (V) L Comprising the amino acid sequence SEQ ID NO. 69 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 69;
    (x)V H comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 70 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 70;
    (xi)V H comprising the amino acid sequence SEQ ID NO. 55 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 55; v (V) L Comprising the amino acid sequence SEQ ID NO. 71 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 71;
    (xii)V H comprising the amino acid sequence SEQ ID NO. 56 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 56; v (V) L Comprising the amino acid sequence SEQ ID NO. 72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 72;
    (xiii)V H comprising the amino acid sequence SEQ ID NO. 57 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 57; v (V) L Comprising the amino acid sequence SEQ ID NO. 73 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 73;
    (xiv)V H comprising the amino acid sequence SEQ ID NO. 58 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 58; v (V) L Comprising the amino acid sequence SEQ ID NO. 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 63;
    (xv)V H comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 74 or a variant thereofA variant having at least about 80% sequence identity to amino acid sequence SEQ ID NO. 74;
    (xvi)V H comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 75 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 75;
    (xvii)V H comprising the amino acid sequence SEQ ID NO. 59 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 59; v (V) L Comprising the amino acid sequence SEQ ID NO. 76 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 76;
    (xviii)V H comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 51; v (V) L Comprising the amino acid sequence SEQ ID NO. 77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 77;
    (xix)V H comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 78;
    (xx)V H comprising the amino acid sequence SEQ ID NO. 52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 52; v (V) L Comprising the amino acid sequence SEQ ID NO. 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 79;
    (xxi)V H comprising the amino acid sequence SEQ ID NO. 51 or a variant thereof, said variant being identical to the amino acid sequence SEQ ID NO. 51 has at least about 80% sequence identity; v (V) L Comprising the amino acid sequence SEQ ID NO. 80 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 80;
    (xxii)V H comprising the amino acid sequence SEQ ID NO. 60 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 60; v (V) L Comprising the amino acid sequence SEQ ID NO. 81 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 81;
    (xxiii)V H comprising the amino acid sequence SEQ ID NO. 56 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 56; v (V) L Comprising the amino acid sequence SEQ ID NO. 82 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 82; or (b)
    (xxiv)V H Comprising the amino acid sequence SEQ ID NO. 61 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 61; v (V) L Comprising the amino acid sequence SEQ ID NO. 66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO. 66.
  9. An isolated antibody that specifically binds FcRn that competes with the isolated anti-FcRn antibody of any one of claims 1-8 for binding to FcRn or specifically binds the same epitope as the isolated anti-FcRn antibody of any one of claims 1-8.
  10. The isolated anti-FcRn antibody of any one of claims 1-9, wherein the anti-FcRn antibody comprises an Fc fragment.
  11. An isolated anti-FcRn antibody according to claim 10, wherein the anti-FcRn antibody is a full length IgA, igD, igE, igG or IgM antibody.
  12. An isolated anti-FcRn antibody according to claim 11, wherein the anti-FcRn antibody is a full length IgG1, igG2, igG3 or IgG4 antibody.
  13. The isolated anti-FcRn antibody of any one of claims 1-12, wherein the anti-FcRn antibody is chimeric, fully human or humanized.
  14. The isolated anti-FcRn antibody of any one of claims 1-9, wherein the anti-FcRn antibody is an antigen binding fragment selected from the group consisting of Fab, fab ', F (ab) '2, fab ' -SH, single chain antibody (scFv), fv fragment, dAb, fd, nanobody, diabody, and linear antibody.
  15. A nucleic acid molecule encoding the anti-FcRn antibody of any one of claims 1-14.
  16. A vector comprising the nucleic acid molecule of claim 15.
  17. An isolated host cell comprising the anti-FcRn antibody of any one of claims 1-14, the nucleic acid molecule of claim 15, or the vector of claim 16.
  18. A method of making an anti-FcRn antibody comprising:
    a) Culturing the host cell of claim 17 under conditions effective to express an anti-FcRn antibody; and is also provided with
    b) Obtaining the expressed anti-FcRn antibody from the host cell.
  19. A pharmaceutical composition comprising an anti-FcRn antibody of any one of claims 1-14, a nucleic acid molecule of claim 15, a vector of claim 16, an isolated host cell of claim 17, or an antibody prepared by the method of claim 18, and a pharmaceutically acceptable carrier.
  20. Use of an antibody according to any one of claims 1-14, a nucleic acid molecule according to claim 15, a vector according to claim 16, a host cell according to claim 17, an antibody produced by a method according to claim 18, or a pharmaceutical composition according to claim 19 for the preparation of a medicament for the treatment of a disease or disorder in a subject in need thereof.
  21. Use according to claim 20, wherein the disease or condition is an autoimmune and/or inflammatory disease.
  22. The use according to claim 21 wherein the disease or condition is selected from the group consisting of myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, guillain-barre syndrome, lupus, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, rheumatoid arthritis, systemic lupus erythematosus, graves 'disease, autoimmune myocarditis, membranous glomerulonephritis, diabetes mellitus type I or type II diabetes, multiple sclerosis, raynaud's syndrome, autoimmune thyroiditis, gastritis, celiac disease, vitiligo, hepatitis, primary biliary cirrhosis, inflammatory bowel disease, spondyloarthropathies, experimental autoimmune encephalomyelitis, immune neutropenia, juvenile onset diabetes, immune responses associated with T-lymphocyte mediated delayed hypersensitivity reactions common in cytokines, tuberculosis, sarcoidosis and polymyositis, polyarteritis, cutaneous vasculitis, pemphigus, phosphotides, systemic sclerosis and anti-inflammatory syndromes.
CN202280003350.6A 2021-09-03 2022-09-02 Antibodies specifically recognizing FcRn and uses thereof Pending CN116234827A (en)

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CN202111031030 2021-09-03
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EP3670538A1 (en) * 2008-04-25 2020-06-24 Dyax Corp. Antibodies against fcrn and use thereof
WO2016123521A2 (en) * 2015-01-30 2016-08-04 Momenta Pharmaceuticals, Inc. Fcrn antibodies and methods of use thereof
EP3294335B1 (en) * 2015-05-12 2023-07-05 Syntimmune Inc. Humanized affinity matured anti-fcrn antibodies
DK3491025T3 (en) * 2016-07-29 2024-01-15 Momenta Pharmaceuticals Inc FCRN ANTIBODIES AND METHODS OF USING THEREOF
JP7420720B2 (en) * 2017-12-13 2024-01-23 モメンタ ファーマシューティカルズ インコーポレイテッド FcRn antibodies and their use

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