TW201945026A - Antibodies binding ERFE and methods of use - Google Patents

Abstract

Provided herein are antibodies that specifically bind to ERFE having variable heavy chain domains (VH), variable light chain domains (VL), and complementarity determining regions disclosed herein, as well as methods and uses in treating diseases and disorders of iron metabolism.

Description

ERFE-binding antibodies and methods of use

Red iron-rich hormone (ERFE) is a protein hormone produced by red blood cells. ERFE inhibits the production of hepcidin, thereby increasing iron content. Thus, modulation of ERFE activity can be used to modulate iron content in an individual, such as an individual suffering from an iron metabolic disease or disorder. Antibodies that bind to ERFE and modulate its activity are desirable for the development of novel therapeutic agents for treating iron metabolic diseases or disorders.

This article discloses monoclonal antibodies that specifically bind to ERFE and thereby regulate ERFE activity, including regulating hepcidin and iron content. These antibodies have been found to bind to ERFE.

Provided herein is a monoclonal antibody or an antigen-binding fragment thereof comprising an amino acid comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The light chain variable domain (VL) of the sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 90% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 95% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 99% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine group comprising 100% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of an acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 90% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 95% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 99% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine group comprising 100% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 Heavy chain variable domain (VH) of an acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 19 and comprising a light chain variable domain (VL) comprising SEQ ID NO: 19 20 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 21 and comprising a light chain variable domain (VL) comprising SEQ ID NO: 21 22 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 23 and comprising a light chain variable domain (VL) identical to SEQ ID NO: 23 24 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof specifically binds to an ERFE protein. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof is selected from the group consisting of whole immunoglobulin, scFv, Fab, F (ab ') ₂ or disulfide-linked Fv. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof is IgG or IgM. In some embodiments, the monoclonal antibodies or fragments thereof are humanized or chimeric.

Also provided herein is a monoclonal antibody or antigen-binding fragment thereof comprising an amine group comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 Heavy chain variable domain (VH) of an acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 90% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 95% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 99% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine group comprising 100% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 Heavy chain variable domain (VH) of an acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 90% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 95% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 99% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine group comprising 100% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of an acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 20 and comprising a heavy chain variable domain (VH) comprising SEQ ID NO: 20 19 Light chain variable domain (VL) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 22 and comprising a heavy chain variable domain (VH) comprising SEQ ID NO: 22 21 Light chain variable domain (VL) with amino acid sequence identity of at least 80%. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 24 and comprising a heavy chain variable domain (VH) comprising SEQ ID NO: 24 23 Light chain variable domain (VL) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof specifically binds to an ERFE protein. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof is selected from the group consisting of whole immunoglobulin, scFv, Fab, F (ab ') ₂ or disulfide-linked Fv. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof is IgG or IgM. In some embodiments, the monoclonal antibodies or fragments thereof are humanized or chimeric.
CDR sequence

Also provided herein is a monoclonal antibody or an antigen-binding fragment thereof, comprising an antibody having at least 80% identity to at least one of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15. Light chain complementarity determining region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least 90% identity to at least one of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15 Light chain complementarity determining region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least 95% identity to at least one of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15 Light chain complementarity determining region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least 99% identity to at least one of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15 Light chain complementarity determining region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a 100% identity with at least one of the amino acid sequences as described in SEQ ID NOs: 1-3, 7-9, and 13-15. Light chain complementarity determining region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least 80% identity to at least one of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18 Heavy chain complementarity determining region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determination that has at least 90% identity to an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determination that has at least 95% identity to an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determination that has at least 99% identity to an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region having 100% identity to an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 having at least 80% identity to one of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 13. (CDR1) sequence, a light chain complementarity determining region 2 (CDR2) sequence having at least 80% identity to one of SEQ ID NO: 2, SEQ ID NO: 8, or SEQ ID NO: 14, and SEQ ID NO: 3.A light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with one of SEQ ID NO: 9 or SEQ ID NO: 15, which is identical to SEQ ID NO: 4, SEQ ID NO: 10, or SEQ ID One of NO: 16 has a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical, and has at least 80 of one of SEQ ID NO: 5, SEQ ID NO: 11, or SEQ ID NO: 17 Heavy chain complementarity determining region 2 (CDR2) sequence with% identity and heavy chain complementarity determining region 3 having at least 80% identity to one of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 13 (CDR3) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 1, and at least 80% identity with SEQ ID NO: 2. The light chain complementarity determining region 2 (CDR2) sequence of sex and the light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 3. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 31. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 32. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 33. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 34. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 7, and at least 80% identity with SEQ ID NO: 8. The light chain complementarity determining region 2 (CDR2) sequence of sex and the light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 9. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 13 and at least 80% identity with SEQ ID NO: 14 The light chain complementarity determining region 2 (CDR2) sequence of sex and the light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity to SEQ ID NO: 15. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 43. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 44. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 45. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 46. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 4, and at least 80% identical to SEQ ID NO: 5. The heavy chain complementarity determining region 2 (CDR2) sequence and the heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 6. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 35. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 36. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 37. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 38. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 10 and at least 80% identical to SEQ ID NO: 11 The heavy chain complementarity determining region 2 (CDR2) sequence of sex and the heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 12. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 39. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 40. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 41. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 42. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 16 and at least 80% identical to SEQ ID NO: 17 The heavy chain complementarity determining region 2 (CDR2) sequence and the heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 18. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 47. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 48. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 49. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 50. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 51. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 52. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 53. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 54. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of an amino acid sequence; and an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 Heavy chain variable domain (VH) of an amino acid sequence; and an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 19 and comprising a light chain variable domain (VL) comprising SEQ ID NO: 19 20 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 21 and comprising a light chain variable domain (VL) comprising SEQ ID NO: 21 22 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 23 and comprising a light chain variable domain (VL) identical to SEQ ID NO: 23 24 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof specifically binds to an ERFE protein. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof is selected from the group consisting of whole immunoglobulin, scFv, Fab, F (ab ') ₂ or disulfide-linked Fv. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof is IgG or IgM. In some embodiments, the monoclonal antibodies or fragments thereof are humanized or chimeric.

Also provided herein are monoclonal antibodies or antigen-binding fragments thereof, including those having at least 80% identity to at least one of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18. Heavy chain complementarity determining region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment comprises an antibody having at least 90% identity to at least one of the amino acid sequences as described in SEQ ID NOs: 4-6, 10-12, and 16-18. Heavy chain complementarity determining region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment comprises an antibody having at least 95% identity to at least one of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18. Heavy chain complementarity determining region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment comprises an antibody having at least 99% identity to at least one of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18. Heavy chain complementarity determining region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment comprises a heavyweight that is 100% identical to at least one of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18. Strand complementarity determining region (CDR) sequences. In some embodiments, the monoclonal antibody or antigen-binding fragment comprises an antibody having at least 80% identity to at least one of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15. Light chain complementarity determining region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determination that has at least 90% identity to an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determination that has at least 95% identity to an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determination that has at least 99% identity to an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Region (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region having 100% identity to an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 (CDR) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 having at least 80% identity to one of SEQ ID NO: 4, SEQ ID NO: 10, or SEQ ID NO: 16 (CDR1) sequence, heavy chain complementarity determining region 2 (CDR2) sequence with at least 80% identity to one of SEQ ID NO: 5, SEQ ID NO: 11 or SEQ ID NO: 17 and SEQ ID NO: 1. A heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with one of SEQ ID NO: 7 or SEQ ID NO: 13, and is identical to SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID One of NO: 13 has at least 80% identity to the light chain complementarity determining region 1 (CDR1) sequence, and one of SEQ ID NO: 2, SEQ ID NO: 8, or SEQ ID NO: 14 has at least 80 Light chain complementarity determining region 2 (CDR2) sequence of% identity and light chain complementarity determining region 3 having at least 80% identity to one of SEQ ID NO: 3, SEQ ID NO: 9 or SEQ ID NO: 15 (CDR3) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 4, and at least 80% identical to SEQ ID NO: 5. The heavy chain complementarity determining region 2 (CDR2) sequence and the heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 6. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 35. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 36. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 37. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 38. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 10 and at least 80% identical to SEQ ID NO: 11 The heavy chain complementarity determining region 2 (CDR2) sequence of sex and the heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 12. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 39. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 40. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 41. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 42. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 16 and at least 80% identical to SEQ ID NO: 17 The heavy chain complementarity determining region 2 (CDR2) sequence and the heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 18. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 47. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 48. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 49. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 50. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 51. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 52. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 53. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 54. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 1 and at least 80% identical to SEQ ID NO: 2 The light chain complementarity determining region 2 (CDR2) sequence of sex and the light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 3. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 31. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 32. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 33. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 34. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 7, and at least 80% identity with SEQ ID NO: 8. The light chain complementarity determining region 2 (CDR2) sequence of sex and the light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 9. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 13 and at least 80% identity with SEQ ID NO: 14 The light chain complementarity determining region 2 (CDR2) sequence of sex and the light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity to SEQ ID NO: 15. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 43. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 44. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 45. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 46. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 Heavy chain variable domain (VH) of an amino acid sequence; and an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 19 and comprising a light chain variable domain (VL) comprising SEQ ID NO: 19 20 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 21 and comprising a light chain variable domain (VL) comprising SEQ ID NO: 21 22 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 23 and comprising a light chain variable domain (VL) identical to SEQ ID NO: 23 24 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof specifically binds to an ERFE protein. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof is selected from the group consisting of whole immunoglobulin, scFv, Fab, F (ab ') ₂ or disulfide-linked Fv. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof is IgG or IgM. In some embodiments, the monoclonal antibodies or fragments thereof are humanized or chimeric.
Treatment method / use

Provided herein is a method of treating an iron metabolism disease or disorder in a subject in need thereof, comprising administering an effective amount of any of the monoclonal antibodies provided herein.

Also provided herein is a method of treating an iron metabolism disease or disorder in an individual in need thereof, comprising administering to the individual an effective amount of a monoclonal antibody, thereby treating an iron metabolism disease or disorder, wherein the monoclonal antibody comprises a compound such as SEQ ID NO: At least one of the amino acid sequences described in 1-3, 7-9, and 13-15 has a light chain complementarity determining region (CDR) sequence that is at least 80% identical. Further provided herein is a method of treating an iron metabolism disease or disorder in an individual in need thereof, comprising administering to the individual an effective amount of a monoclonal antibody, thereby treating the iron metabolism disease or disorder, wherein the monoclonal antibody comprises a compound such as SEQ ID NO: At least one of the amino acid sequences described in 4-6, 10-12, and 16-18 has a heavy chain complementarity determining region (CDR) sequence that is at least 80% identical. In some embodiments, the monoclonal antibody comprises a) a light chain that is at least 80% identical to at least one of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15 Complementarity determining region (CDR) sequences; and b) a heavy chain complementary to at least 80% identity to at least one of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18 Determinant region (CDR) sequence. In some embodiments, the monoclonal antibody comprises a) a light chain having at least 80% identity to at least two of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15 Complementarity determining region (CDR) sequences; and b) a heavy chain complementary to at least 80% identity to at least two of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18 Determinant region (CDR) sequence. In some embodiments, the monoclonal antibody comprises a) a light chain complementarity determining region (CDR) having at least 90% identity to an amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 ) Sequence; and b) a heavy chain complementarity determining region (CDR) sequence having at least 90% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18. In some embodiments, the monoclonal antibody comprises a) a light chain complementarity determining region (CDR) having at least 95% identity to an amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 ) Sequence; and b) a heavy chain complementarity determining region (CDR) sequence having at least 95% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18. In some embodiments, the monoclonal antibody comprises a) a light chain complementarity determining region (CDR) having at least 99% identity to an amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 ) Sequence; and b) a heavy chain complementarity determining region (CDR) sequence having at least 99% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18. In some embodiments, the monoclonal antibody comprises a) a light chain complementarity determining region (CDR) having 100% identity to an amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 ) Sequence; and b) a heavy chain complementarity determining region (CDR) sequence having 100% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 having at least 80% identity to one of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 13. (CDR1) sequence, a light chain complementarity determining region 2 (CDR2) sequence having at least 80% identity to one of SEQ ID NO: 2, SEQ ID NO: 8, or SEQ ID NO: 14, and SEQ ID NO: 3.A light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with one of SEQ ID NO: 9 or SEQ ID NO: 15, which is identical to SEQ ID NO: 4, SEQ ID NO: 10, or SEQ ID One of NO: 16 has a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical, and has at least 80 of one of SEQ ID NO: 5, SEQ ID NO: 11, or SEQ ID NO: 17 Heavy chain complementarity determining region 2 (CDR2) sequence with% identity and heavy chain complementarity determining region 3 having at least 80% identity to one of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 13 (CDR3) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 1 and at least 80% identical to SEQ ID NO: 2 The light chain complementarity determining region 2 (CDR2) sequence of sex and the light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 3. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 31. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 32. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 33. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 34. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 7, and at least 80% identity with SEQ ID NO: 8. The light chain complementarity determining region 2 (CDR2) sequence of sex and the light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 9. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 13 and at least 80% identity with SEQ ID NO: 14 The light chain complementarity determining region 2 (CDR2) sequence of sex and the light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity to SEQ ID NO: 15. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 43. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 44. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 45. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 46. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 4, and at least 80% identical to SEQ ID NO: 5. The heavy chain complementarity determining region 2 (CDR2) sequence and the heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 6. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 35. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 36. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 37. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 38. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 10 and at least 80% identical to SEQ ID NO: 11 The heavy chain complementarity determining region 2 (CDR2) sequence of sex and the heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 12. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 39. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 40. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 41. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 42. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 16 and at least 80% identical to SEQ ID NO: 17 The heavy chain complementarity determining region 2 (CDR2) sequence and the heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 18. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 47. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 48. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 49. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 50. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 51. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 52. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 53. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 54. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of an amino acid sequence; and an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 19 and comprising a light chain variable domain (VL) comprising SEQ ID NO: 19 20 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 21 and comprising a light chain variable domain (VL) comprising SEQ ID NO: 21 22 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 23 and comprising a light chain variable domain (VL) identical to SEQ ID NO: 23 24 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof specifically binds to an ERFE protein. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof is selected from the group consisting of whole immunoglobulin, scFv, Fab, F (ab ') ₂ or disulfide-linked Fv. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof is IgG or IgM. In some embodiments, the monoclonal antibodies or fragments thereof are humanized or chimeric. In some embodiments, administration of a monoclonal antibody increases hepcidin content in an individual. In some embodiments, administration of a monoclonal antibody reduces iron content in an individual. In some embodiments, the iron metabolism disease or disorder is selected from the group consisting of: hemochromatosis, HFE mutation hemochromatosis, transferrin mutation hemochromatosis, transferrin receptor 2 mutation hemochromatosis, iron regulation Hemomodulin Mutation Hemochromatosis, Hepcidin Mutation Hemochromatosis, Adolescent Hemochromatosis, Hemochromatosis, Hepcidin Deficiency, Transfusion Iron Overload, Thalassemia, Intermediate Thalassemia, Alpha Thalassemia , Beta thalassemia, bone marrow dysplasia syndrome, polyanaemia, hemangioblastic anemia, porphyria, delayed skin porphyria, African iron overload, hyperferritinemia, plasma acerin deficiency Iron-free transfer protein anemia. In some embodiments, the method reduces at least one symptom of a disease or disorder of iron metabolism. In some embodiments, the symptoms are selected from the group consisting of: chronic fatigue, joint pain, abdominal pain, liver disease (cirrhosis, liver cancer), diabetes, irregular heart rhythm, heart attack or heart failure, skin color change (bronze, (Light gray green), menstrual loss, loss of libido, osteoarthritis, osteoporosis, hair loss, liver or splenomegaly, impotence, infertility, hypogonadism, hypothyroidism, hypopituitarism, depression, adrenal glands Functional problems, early-onset neurodegenerative diseases, elevated blood sugar, elevated liver enzymes, elevated iron (e.g. serum iron, serum ferritin), excessive iron deposition in the liver, excessive iron deposition in the heart, weakness, pale skin, and shortness of breath , Dizziness, craving for eating, tingling or insect crawling in the legs, swelling or sore tongue, cold hands and feet, fast or irregular heartbeat, crisp nails and headache. In some embodiments, the method further comprises phlebotomy or chelation therapy. In some embodiments, the treated individual no longer needs phlebotomy or chelation therapy to reduce iron content.

Also provided herein are monoclonal antibodies disclosed herein for use in treating iron metabolic diseases or disorders.

Also provided herein are monoclonal antibodies disclosed herein for use in the preparation of a medicament for treating a disease or disorder of iron metabolism.
combination

Also provided herein are compositions comprising a monoclonal antibody or antigen-binding fragment thereof and at least one buffer or excipient, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from any of the monoclonal antibodies provided herein.

Also provided herein is a composition comprising a monoclonal antibody or antigen-binding fragment thereof and at least one buffer or excipient, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a compound such as SEQ ID NOs: 1-3, 7-9, and 13 At least one of the amino acid sequences described in -15 has a light chain complementarity determining region (CDR) sequence that is at least 80% identical. Further provided herein is a composition comprising a monoclonal antibody or an antigen-binding fragment thereof and at least one buffer or excipient, wherein the monoclonal antibody or the antigen-binding fragment thereof comprises a compound such as SEQ ID NOs: 4-6, 10-12, and 16 At least one of the amino acid sequences described in -18 has a heavy chain complementarity determining region (CDR) sequence that is at least 80% identical. In some embodiments, the monoclonal antibody comprises a) a light chain that is at least 80% identical to at least one of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15 Complementarity determining region (CDR) sequences; and b) a heavy chain complementary to at least 80% identity to at least one of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18 Determinant region (CDR) sequence. In some embodiments, the monoclonal antibody comprises a) a light chain having at least 80% identity to at least two of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15 Complementarity determining region (CDR) sequences; and b) a heavy chain complementary to at least 80% identity to at least two of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18 Determinant region (CDR) sequence. In some embodiments, the monoclonal antibody comprises a) a light chain complementarity determining region (CDR) having at least 90% identity to an amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 ) Sequence; and b) a heavy chain complementarity determining region (CDR) sequence having at least 90% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18. In some embodiments, the monoclonal antibody comprises a) a light chain complementarity determining region (CDR) having at least 95% identity to an amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 ) Sequence; and b) a heavy chain complementarity determining region (CDR) sequence having at least 95% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18. In some embodiments, the monoclonal antibody comprises a) a light chain complementarity determining region (CDR) having at least 99% identity to an amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 ) Sequence; and b) a heavy chain complementarity determining region (CDR) sequence having at least 99% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18. In some embodiments, the monoclonal antibody comprises a) a light chain complementarity determining region (CDR) having 100% identity to an amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 Sequence; and b) a heavy chain complementarity determining region (CDR) sequence having 100% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 having at least 80% identity to one of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 13. (CDR1) sequence, a light chain complementarity determining region 2 (CDR2) sequence having at least 80% identity to one of SEQ ID NO: 2, SEQ ID NO: 8, or SEQ ID NO: 14, and SEQ ID NO: 3.A light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with one of SEQ ID NO: 9 or SEQ ID NO: 15, which is identical to SEQ ID NO: 4, SEQ ID NO: 10, or SEQ ID One of NO: 16 has a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical, and has at least 80 of one of SEQ ID NO: 5, SEQ ID NO: 11, or SEQ ID NO: 17 Heavy chain complementarity determining region 2 (CDR2) sequence with% identity and heavy chain complementarity determining region 3 having at least 80% identity to one of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 13 (CDR3) sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 1 and at least 80% identical to SEQ ID NO: 2 The light chain complementarity determining region 2 (CDR2) sequence of sex and the light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 3. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 31. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 32. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 33. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 34. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 7, and at least 80% identity with SEQ ID NO: 8. The light chain complementarity determining region 2 (CDR2) sequence of sex and the light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 9. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 13 and at least 80% identity with SEQ ID NO: 14 The light chain complementarity determining region 2 (CDR2) sequence of sex and the light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity to SEQ ID NO: 15. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 43. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 44. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 45. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 46. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 4, and at least 80% identical to SEQ ID NO: 5. The heavy chain complementarity determining region 2 (CDR2) sequence and the heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 6. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 35. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 36. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 37. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 38. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 10 and at least 80% identical to SEQ ID NO: 11 The heavy chain complementarity determining region 2 (CDR2) sequence of sex and the heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 12. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 39. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 40. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 41. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 42. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 16 and at least 80% identical to SEQ ID NO: 17 The heavy chain complementarity determining region 2 (CDR2) sequence and the heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 18. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 47. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 48. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 49. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 50. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 51. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 52. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 53. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 54. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of an amino acid sequence; and an amine comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 19 and comprising a light chain variable domain (VL) comprising SEQ ID NO: 19 20 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 21 and comprising a light chain variable domain (VL) comprising SEQ ID NO: 21 22 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 23 and comprising a light chain variable domain (VL) identical to SEQ ID NO: 23 24 Heavy chain variable domain (VH) with an amino acid sequence that is at least 80% identical. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof specifically binds to an ERFE protein. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof is selected from the group consisting of whole immunoglobulin, scFv, Fab, F (ab ') ₂ or disulfide-linked Fv. In some embodiments, the monoclonal antibody or antigen-binding fragment thereof is IgG or IgM. In some embodiments, the monoclonal antibodies or fragments thereof are humanized or chimeric.

Monoclonal antibodies disclosed herein that specifically bind to ERFE to modulate serum iron content in individuals and treat iron metabolic diseases or disorders.
ERFE antibody

Provided herein are antibodies that specifically bind to ERFE or ERFE fragments. In some embodiments, the ERFE antibody comprises at least one heavy chain comprising a heavy chain variable domain (VH) and at least one light chain comprising a light chain variable domain (VL). VH and VL each contain three complementary determining regions (CDRs). The amino acid sequences of VH, VL and CDR determine the antigen-binding specificity and antigen-binding strength of the antibody.

In some embodiments, an anti-systemic monoclonal antibody that specifically binds to an ERFE or ERFE fragment. In some embodiments, the anti-system antigen-binding fragment. In some embodiments, the anti-system is selected from whole immunoglobulin, scFv, Fab, F (ab ') 2, or disulfide-linked Fv. In some embodiments, the system is IgG or IgM. In some embodiments, the system is IgG1. In some embodiments, the anti-system is humanized. In some embodiments, the antibody system is chimeric.
ERFE antibody variable domain

Disclosed herein are antibodies that specifically bind to ERFE and have a heavy chain comprising a heavy chain variable domain (VH). In some embodiments, the antibody that binds to the ERFE comprises an amino acid having at least about 70% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the sequence. In some embodiments, VH has an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 having at least about 75%, 80%, 81%, 82%, 83 %, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% Sexual amino acid sequence. In some embodiments, the VH has an amino acid sequence that is 100% identical to the amino acid sequence described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24.

Further disclosed herein are antibodies that specifically bind to ERFE and have a light chain comprising a light chain variable domain (VL). In some embodiments, an antibody that binds to an ERFE comprises an amino acid having at least about 70% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The light chain variable domain (VL) of the sequence. In some embodiments, VL has an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 that has at least about 75%, 80%, 81%, 82%, 83 %, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% Sexual amino acid sequence. In some embodiments, VL has an amino acid sequence that is 100% identical to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23.

Also disclosed herein are antibodies that bind to ERFE and include a heavy chain variable domain (VH) and a light chain variable domain (VL). In some embodiments, an antibody that binds to an ERFE comprises an amino acid sequence having at least about 70% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 Heavy chain variable domain (VH) and an amino acid having at least about 70% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21 or SEQ ID NO: 23 The light chain variable domain (VL) of the sequence. In some embodiments, VH has an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 having at least about 75%, 80%, 81%, 82%, 83 %, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% Amino acid sequence, and VL has at least about 75%, 80%, 81%, 82% of the amino acid sequence described in SEQ ID NO: 19, SEQ ID NO: 21 or SEQ ID NO: 23 , 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99 % Identical amino acid sequences. In some embodiments, VH has an amino acid sequence that is 100% identical to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24, and VL has an amino acid sequence as The amino acid sequence described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 has an amino acid sequence that is 100% identical.

Also disclosed herein is an antibody that binds to ERFE, comprising a heavy chain variable domain (VH) comprising an amino acid sequence having at least about 70% identity to SEQ ID NO: 20 and comprising an antibody having at least about 70% identity to SEQ ID NO: 20 The light chain variable domain (VL) of the amino acid sequence is approximately 70% identical. In some embodiments, VH has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87% of the amino acid sequence as described in SEQ ID NO: 20 %, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity amino acid sequences, and VL has an amino acid sequence such as The amino acid sequence described in SEQ ID NO: 19 has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90% , 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical amino acid sequences. In some embodiments, VH has an amino acid sequence that is 100% identical to the amino acid sequence as described in SEQ ID NO: 20, and VL has an amino acid sequence as described in SEQ ID NO: 19 Amino acid sequence with 100% identity.

Also disclosed herein is an antibody that binds to ERFE, comprising a heavy chain variable domain (VH) comprising an amino acid sequence having at least about 70% identity to SEQ ID NO: 22 and comprising an antibody having at least about 70% identity to SEQ ID NO: 21 The light chain variable domain (VL) of the amino acid sequence is approximately 70% identical. In some embodiments, VH has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87% of the amino acid sequence as described in SEQ ID NO: 22 %, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity amino acid sequences, and VL has The amino acid sequence described in SEQ ID NO: 21 has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90% , 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical amino acid sequences. In some embodiments, VH has an amino acid sequence with 100% identity to the amino acid sequence described in SEQ ID NO: 22 and VL has an amino acid sequence with the amino acid sequence described in SEQ ID NO: 21 100% identical amino acid sequences.

Also disclosed herein is an antibody that binds to ERFE, comprising a heavy chain variable domain (VH) comprising an amino acid sequence having at least about 70% identity to SEQ ID NO: 24 and comprising an antibody having at least about 70% identity to SEQ ID NO: 23 The light chain variable domain (VL) of the amino acid sequence is approximately 70% identical. In some embodiments, VH has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87% of amino acid sequence as described in SEQ ID NO: 24. %, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity amino acid sequences, and VL has The amino acid sequence described in SEQ ID NO: 23 has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90% , 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical amino acid sequences. In some embodiments, VH has an amino acid sequence with 100% identity to the amino acid sequence described in SEQ ID NO: 24 and VL has an amino acid sequence with the amino acid sequence described in SEQ ID NO: 23 100% identical amino acid sequences.
ERFE antibody complementarity determining region

Disclosed herein are antibodies that specifically bind to ERFE and have a heavy chain comprising a heavy chain complementarity determining region (CDR). In some embodiments, the antibody that binds to the ERFE comprises an amino acid having at least about 70% identity to at least one amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 The heavy chain CDRs of the sequence. In some embodiments, the heavy chain CDR has at least about 75%, 80%, 81%, 82% of at least one amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 , 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99 % Identical amino acid sequences. In some embodiments, the heavy chain CDR has an amino acid sequence that is 100% identical to at least one amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18.

Further disclosed herein are antibodies that specifically bind to ERFE and have a light chain comprising a light chain complementarity determining region (CDR). In some embodiments, the antibody that binds to ERFE comprises an amino acid having at least about 70% identity to at least one amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 The light chain CDRs of the sequence. In some embodiments, the light chain CDR has at least about 75%, 80%, 81%, 82% of at least one amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 , 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99 % Identical amino acid sequences. In some embodiments, the light chain CDR has an amino acid sequence that is 100% identical to at least one amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15.

Also disclosed herein are antibodies that bind to an ERFE and include a heavy chain complementarity determining region (CDR) and a light chain complementarity determining region (CDR). In some embodiments, the antibody that binds to the ERFE comprises an amino acid having at least about 70% identity to at least one amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 A heavy chain CDR of the sequence and a light chain CDR having an amino acid sequence having at least about 70% identity to at least one amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15. In some embodiments, the heavy chain CDR has at least about 75%, 80%, 81%, 82% of at least one amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 , 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99 % Amino acid sequence, and the light chain CDR has at least about 75%, 80%, 81% of at least one amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 %, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical amino acid sequences. In some embodiments, the heavy chain CDR has an amino acid sequence that is 100% identical to at least one amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18, and the light chain The CDR has an amino acid sequence that is 100% identical to at least one amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15.

In some embodiments, the antibody that binds to ERFE comprises an amine having at least about 70% identity to at least one amino acid sequence as described in SEQ ID NO: 4, SEQ ID NO: 10, or SEQ ID NO: 16 The heavy chain CDR1 of the amino acid sequence has the same structure as SEQ ID NO: 5, SEQ ID NO: 11, SEQ ID NO: 17, SEQ ID NO: 35-38, SEQ ID NO: 39-42, or SEQ ID NO: 47 The heavy chain CDR2 of at least one amino acid sequence described in -54 has an amino acid sequence of at least about 70% identity, has the same sequence as described in SEQ ID NO: 6, SEQ ID NO: 12, or SEQ ID NO: 18 The heavy chain CDR3 of at least one amino acid sequence having an amino acid sequence that is at least about 70% identical, has the same sequence as SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 13, SEQ ID NO: 31 -32 or SEQ ID NO: 43-46, at least one amino acid sequence having at least about 70% identity of the light chain CDR1 of the amino acid sequence, has the same as SEQ ID NO: 2, SEQ ID NO: 8 Light chain CDRs of at least one amino acid sequence described in SEQ ID NO: 14 or SEQ ID NOs: 33-34 having at least about 70% identity to an amino acid sequence; Up to SEQ ID NO: 9 or SEQ ID NO: 15 An amino acid sequence having at least about 70% amino acid sequence identity of a light chain CDR3. In some embodiments, the antibody that binds to the ERFE comprises a compound having at least about 75%, 80%, at least one amino acid sequence as described in SEQ ID NO: 4, SEQ ID NO: 10, or SEQ ID NO: 16. 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% , 98% or 99% identity of the amino acid sequence of the heavy chain CDR1, with the same as SEQ ID NO: 5, SEQ ID NO: 11, SEQ ID NO: 17, SEQ ID NO: 35-38, SEQ ID NO : 39-42 or at least one amino acid sequence described in SEQ ID NOs: 47-54 has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87% Heavy chain CDR2 of an amino acid sequence with 88%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity At least one amino acid sequence as described in SEQ ID NO: 6, SEQ ID NO: 12 or SEQ ID NO: 18 has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85% , 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical amino acid sequences The heavy chain CDR3 has the same sequence as SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 13, SEQ ID NO: 31- 32 or at least one amino acid sequence described in SEQ ID NOs: 43-46 has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88% Light chain CDR1 of an amino acid sequence having the same, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, having the same sequence as SEQ ID NO: 2, SEQ ID NO: 8, SEQ ID NO: 14 or SEQ ID NO: 33-34 has at least one amino acid sequence having at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% The light chain CDR2 of the amino acid sequence has at least about 75%, 80%, 81% of at least one amino acid sequence as described in SEQ ID NO: 3, SEQ ID NO: 9 or SEQ ID NO: 15 , 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98 Light chain CDR3 of amino acid sequence with% or 99% identity. In some embodiments, the antibody that binds to the ERFE comprises an amino acid having 100% identity to at least one amino acid sequence as described in SEQ ID NO: 4, SEQ ID NO: 10, or SEQ ID NO: 16 The heavy chain CDR1 of the sequence has the same sequence as SEQ ID NO: 5, SEQ ID NO: 11, SEQ ID NO: 17, SEQ ID NO: 35-38, SEQ ID NO: 39-42, or SEQ ID NO: 47-54 The at least one amino acid sequence has a heavy chain CDR2 having an amino acid sequence that is 100% identical, and has at least one amine as described in SEQ ID NO: 6, SEQ ID NO: 12, or SEQ ID NO: 18 The CDR3 of the amino acid sequence has a 100% amino acid sequence, and has the same sequence as SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 13, SEQ ID NO: 31-32 or SEQ ID NO : At least one amino acid sequence described in 43-46 has a light chain CDR1 of an amino acid sequence with 100% identity, and has a sequence similar to SEQ ID NO: 2, SEQ ID NO: 8, SEQ ID NO: 14 or SEQ ID NO: 33-34 at least one amino acid sequence has a light chain CDR2 with an amino acid sequence of 100% identity, and has a light chain CDR2 as in SEQ ID NO: 3, SEQ ID NO: 9 or SEQ ID NO: 15 at least one amino acid sequence is 100% identical The light chain CDR3 amino acid sequence.

In some embodiments, an antibody that binds to an ERFE comprises a heavy chain CDR1 having an amino acid sequence that is at least about 70% identical to the amino acid sequence described in SEQ ID NO: 4, : The heavy chain CDR2 of the amino acid sequence having at least about 70% identity with the amino acid sequence described in 5, having an amine having at least about 70% identity with the amino acid sequence according to SEQ ID NO: 6 CDR3 of the heavy chain of the amino acid sequence, light chain CDR1 of the amino acid sequence having at least about 70% identity to the amino acid sequence described in SEQ ID NO: 1, and the same as described in SEQ ID NO: 2 A light chain CDR2 having an amino acid sequence having at least about 70% identity and an amino acid sequence having at least about 70% identity with the amino acid sequence described in SEQ ID NO: 3 Light chain CDR3. In some embodiments, the antibody that binds to the ERFE comprises an amino acid sequence having at least about 75%, 80%, 81%, 82%, 83%, 84%, 85% of the amino acid sequence as described in SEQ ID NO: 4 , 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical amino acid sequences Heavy chain CDR1, having at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88% of the amino acid sequence as described in SEQ ID NO: 5 %, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the amino acid sequence of the heavy chain CDR2, has a The amino acid sequence described in ID NO: 6 has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, Heavy chain CDR3 of an amino acid sequence with 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, with an amine as described in SEQ ID NO: 1 Basic acid sequences have at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93% , 94%, 95%, 96%, 97%, 98%, or 99% identical amino acid sequences of the light chain CDR1, having the same sequence as described in SEQ ID NO: 2 Amino acid sequences have at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93 %, 94%, 95%, 96%, 97%, 98%, or 99% identity of the light chain CDR2 of the amino acid sequence, and having at least about the amino acid sequence described in SEQ ID NO: 3 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95% CDR3 of an amino acid sequence of 96%, 96%, 97%, 98%, or 99% identity. In some embodiments, the antibody that binds to the ERFE comprises a heavy chain CDR1 having an amino acid sequence that is 100% identical to the amino acid sequence described in SEQ ID NO: 4, The amino acid sequence has a heavy chain CDR2 having an amino acid sequence of 100% identity, and the heavy chain having an amino acid sequence having a 100% identity with the amino acid sequence described in SEQ ID NO: 6 CDR3, a light chain CDR1 having an amino acid sequence having 100% identity to the amino acid sequence described in SEQ ID NO: 1, having 100% identity to the amino acid sequence as described in SEQ ID NO: 2 Light chain CDR2 of identical amino acid sequences and light chain CDR3 having an amino acid sequence that is 100% identical to the amino acid sequence described in SEQ ID NO: 3.

In some embodiments, an antibody that binds to an ERFE comprises a heavy chain CDR1 having an amino acid sequence that is at least about 70% identical to the amino acid sequence described in SEQ ID NO: 10, : The heavy chain CDR2 of the amino acid sequence having at least about 70% identity with the amino acid sequence described in 11, having an amine having at least about 70% identity with the amino acid sequence according to SEQ ID NO: 12 CDR3 of heavy chain of amino acid sequence, light chain CDR1 of amino acid sequence having at least about 70% identity with the amino acid sequence described in SEQ ID NO: 7, A light chain CDR2 having an amino acid sequence having at least about 70% identity and an amino acid sequence having at least about 70% identity with the amino acid sequence described in SEQ ID NO: 9 Light chain CDR3. In some embodiments, the antibody that binds to the ERFE comprises an amino acid sequence having at least about 75%, 80%, 81%, 82%, 83%, 84%, 85% of the amino acid sequence as described in SEQ ID NO: 10 , 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical amino acid sequences Heavy chain CDR1, having at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88% of the amino acid sequence as described in SEQ ID NO: 11 %, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the amino acid sequence of the heavy chain CDR2, has a The amino acid sequence described in ID NO: 12 has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, Heavy chain CDR3 of an amino acid sequence with 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, with an amine as described in SEQ ID NO: 7 Basic acid sequences have at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93% The light chain CDR1 of the amino acid sequence, which is 94%, 95%, 96%, 97%, 98%, or 99% identical, has the same structure as SEQ ID NO: 8 The amino acid sequence has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, Light chain CDR2 with an amino acid sequence of 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity and having at least the same amino acid sequence as SEQ ID NO: 9 About 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95 Light chain CDR3 of amino acid sequence with%, 96%, 97%, 98% or 99% identity. In some embodiments, the antibody that binds to the ERFE comprises a heavy chain CDR1 having an amino acid sequence that is 100% identical to the amino acid sequence as described in SEQ ID NO: 10, and having a sequence that is similar to SEQ ID NO: 11 The amino acid sequence has a heavy chain CDR2 having an amino acid sequence of 100% identity, and the heavy chain having an amino acid sequence having a 100% identity with the amino acid sequence described in SEQ ID NO: 12 CDR3, a light chain CDR1 having an amino acid sequence having 100% identity to the amino acid sequence described in SEQ ID NO: 7, having 100% identity to the amino acid sequence as described in SEQ ID NO: 8 Light chain CDR2 of identical amino acid sequences and light chain CDR3 having an amino acid sequence that is 100% identical to the amino acid sequence described in SEQ ID NO: 9.

In some embodiments, an antibody that binds to an ERFE comprises a heavy chain CDR1 having an amino acid sequence having at least about 70% identity to the amino acid sequence as described in SEQ ID NO: 16, : The heavy chain CDR2 of the amino acid sequence having at least about 70% identity with the amino acid sequence described in 17, having an amine having at least about 70% identity with the amino acid sequence according to SEQ ID NO: 18 CDR3 of the heavy chain of the amino acid sequence, light chain CDR1 of the amino acid sequence having at least about 70% identity to the amino acid sequence described in SEQ ID NO: 13, and the same as described in SEQ ID NO: 14 A light chain CDR2 having an amino acid sequence having at least about 70% identity and an amino acid sequence having at least about 70% identity with the amino acid sequence described in SEQ ID NO: 15 Light chain CDR3. In some embodiments, the antibody that binds to the ERFE comprises an amino acid sequence having at least about 75%, 80%, 81%, 82%, 83%, 84%, 85% of the amino acid sequence as described in SEQ ID NO: 16. , 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical amino acid sequences Heavy chain CDR1, having at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88 of the amino acid sequence described in SEQ ID NO: 17 %, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the amino acid sequence of the heavy chain CDR2, has a The amino acid sequence described in ID NO: 18 has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, Heavy chain CDR3 of an amino acid sequence with 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, with an amine as described in SEQ ID NO: 13 Basic acid sequences have at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93% The light chain CDR1 of the amino acid sequence is 94%, 95%, 96%, 97%, 98%, or 99% identical, and has the same structure as SEQ ID NO: 14 The amino acid sequence described has at least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92% , 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical amino acid sequences of light chain CDR2, and having an amino acid sequence as described in SEQ ID NO: 15 having At least about 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, Light chain CDR3 of an amino acid sequence with 95%, 96%, 97%, 98% or 99% identity. In some embodiments, the antibody that binds to ERFE comprises a heavy chain CDR1 having an amino acid sequence that is 100% identical to the amino acid sequence as described in SEQ ID NO: 16 and has a sequence that is similar to SEQ ID NO: 17 The amino acid sequence has a heavy chain CDR2 having an amino acid sequence of 100% identity, and the heavy chain having an amino acid sequence having a 100% identity with the amino acid sequence described in SEQ ID NO: 18 CDR3, a light chain CDR1 having an amino acid sequence with 100% identity to the amino acid sequence described in SEQ ID NO: 13 and 100% with an amino acid sequence as described in SEQ ID NO: 14 Light chain CDR2 of identical amino acid sequences and light chain CDR3 having an amino acid sequence that is 100% identical to the amino acid sequence described in SEQ ID NO: 15.
Diseases and disorders of iron metabolism

Provided herein are methods of treating an iron metabolism disease or disorder in an individual, comprising administering an ERFE antibody disclosed herein. In some embodiments, the iron metabolism disease or disorder comprises a disease or disorder in an individual without abnormal iron content. In some embodiments, a disease or disorder of iron metabolism comprises a disease or disorder of an individual having an abnormally high iron content. In some embodiments, a disease or disorder of iron metabolism comprises a disease or disorder of an individual having an abnormally low iron content. The iron metabolism diseases and disorders herein include (but are not limited to) hemochromatosis, HFE mutation hemochromatosis, transferrin mutation hemochromatosis, transferrin receptor 2 mutation hemochromatosis, hepcidin-regulated protein mutation hemoglobinosis Disease, hepcidin mutation hemochromatosis, adolescent hemochromatosis, neohemochromatosis, hepcidin deficiency, transfusion iron overload, thalassemia, intermediate thalassemia, alpha thalassemia, beta thalassemia, Bone marrow dysplasia, polyanaemia, hemangioblastic anemia, porphyria, delayed skin porphyria, African iron overload, hyperferritinemia, plasma ceruloplasmin deficiency, anemia without iron transfer protein, Congenital anemia with poor erythropoiesis, chronic disease anemia, inflammatory anemia, infection anemia, light-colored small cell anemia, iron deficiency anemia, iron restricted anemia, iron refractory iron deficiency anemia, chronic kidney disease anemia, erythropoietin Resistance, iron deficiency in obesity or another type of anemia.

In some embodiments, a method of treating a disease or disorder of iron metabolism reduces at least one symptom of the disease or disorder of iron metabolism. Symptoms include (but are not limited to) chronic fatigue, joint pain, abdominal pain, liver disease (e.g., sclerosis, liver cancer), diabetes, irregular heart rhythm, heart attack or heart failure, skin color changes (e.g., bronze, light gray-green), menstruation Stage loss, loss of libido, osteoarthritis, osteoporosis, hair loss, liver or splenomegaly, impotence, infertility, hypogonadism, hypothyroidism, hypopituitarism, depression, adrenal function problems, early-onset nerves Degenerative diseases, elevated blood sugar, elevated liver enzymes, elevated iron (e.g. serum iron, serum ferritin), excessive iron deposition in the liver, excessive iron deposition in the heart, weakness, pale skin, shortness of breath, dizziness, craving for diet, Leg tingling or insect crawling, tongue swelling or soreness, cold hands and feet, fast or irregular heartbeat, brittle nails, and headache. In some embodiments, the symptoms are fatigue. In some embodiments, the symptoms are weakness. In some embodiments, the symptoms are pale skin. In some embodiments, the symptoms are shortness of breath. In some embodiments, the symptoms are dizziness.

Any suitable route of administration is encompassed for use with the methods disclosed herein. In some embodiments, the antibody system is administered by intravenous administration. In some embodiments, the anti-system is administered by subcutaneous administration. In some embodiments, the anti-system is administered locally. In some embodiments, the antibody system is administered systemically (eg, intravenously, intramuscularly, subcutaneously, intradermally, orally, intranasally, sublingually). In some embodiments, the antibody is formulated as a salve, lotion or emulsion. In some embodiments, the antibody is formulated as a solution. In some embodiments, the antibody is formulated for topical, oral, buccal, or nasal administration.

In some embodiments, the individual is monitored before the antibody is administered. Identify symptoms and evaluate their severity. Antibodies as described herein are administered alone or in combination with additional treatments, as discussed herein or known to those skilled in the art, in single or multiple administrations over time. In some embodiments, the individual is monitored such that the efficacy of a treatment regimen is determined. In some embodiments, the treatment regimen is modified in accordance with the initial treatment results such that the therapeutic dose or frequency or dose and frequency is changed in order to obtain the desired level of individual response in view of the relief of symptoms, reduced side effects, or a combination of symptom relief and reduced side effects.

A therapeutically effective amount or dose is encompassed to include a dose of about 0.01 mg / kg to about 20 mg / kg, for example, about 0.01 mg / kg, about 0.02 mg / kg, about 0.03 mg / kg, about 0.04 mg / kg, about 0.05 mg / kg, about 0.06 mg / kg, about 0.07 mg / kg, about 0.08 mg / kg, about 0.09 mg / kg, about 0.1 mg / kg, about 0.2 mg / kg, about 0.3 mg / kg, about 0.4 mg / kg, about 0.5 mg / kg, about 0.6 mg / kg, about 0.7 mg / kg, about 0.8 mg / kg, about 0.9 mg / kg, about 1.0 mg / kg, about 1.1 mg / kg, about 1.2 mg / kg , About 1.3 mg / kg, about 1.4 mg / kg, about 1.5 mg / kg, about 1.6 mg / kg, about 1.7 mg / kg, about 1.8 mg / kg, about 1.9 mg / kg, about 2 mg / kg, about 2.1 mg / kg, about 2.2 mg / kg, about 2.3 mg / kg, about 2.4 mg / kg, about 2.5 mg / kg, about 2.6 mg / kg, about 2.7 mg / kg, about 2.8 mg / kg, about 2.9 mg / kg, about 3 mg / kg, about 3.1 mg / kg, about 3.2 mg / kg, about 3.3 mg / kg, about 3.4 mg / kg, about 3.5 mg / kg, about 3.6 mg / kg, about 3.7 mg / kg , About 3.8 mg / kg, about 3.9 mg / kg, about 4 mg / kg, about 4.1 mg / kg, about 4.2 mg / kg, about 4.3 mg / kg, about 4.4 mg / kg, about 4.5 mg / kg, about 4.6 mg / kg, about 4.7 mg / kg, about 4.8 mg / kg, about 4.9 mg / kg, about 5 mg / kg, about 5.1 mg / kg, about 5.2 mg / kg, about 5.3 mg / kg, about 5.4 mg / kg, about 5.5 mg / kg, about 5.6 mg / kg, about 5.7 mg / kg, about 5.8 mg / kg, about 5.9 mg / kg, about 6 mg / kg kg, about 6.1 mg / kg, about 6.2 mg / kg, about 6.3 mg / kg, about 6.4 mg / kg, about 6.5 mg / kg, about 6.6 mg / kg, about 6.7 mg / kg, about 6.8 mg / kg, About 6.9 mg / kg, about 7 mg / kg, about 7.1 mg / kg, about 7.2 mg / kg, about 7.3 mg / kg, about 7.4 mg / kg, about 7.5 mg / kg, about 7.6 mg / kg, about 7.7 mg / kg, about 7.8 mg / kg, about 7.9 mg / kg, about 8 mg / kg, about 8.1 mg / kg, about 8.2 mg / kg, about 8.3 mg / kg, about 8.4 mg / kg, about 8.5 mg / kg, about 8.6 mg / kg, about 8.7 mg / kg, about 8.8 mg / kg, about 8.9 mg / kg, about 9 mg / kg, about 9.1 mg / kg, about 9.2 mg / kg, about 9.3 mg / kg, About 9.4 mg / kg, about 9.5 mg / kg, about 9.6 mg / kg, about 9.7 mg / kg, about 9.8 mg / kg, about 9.9 mg / kg, about 10 mg / kg, about 10.1 mg / kg, about 10.2 mg / kg, about 10.3 mg / kg, about 10.4 mg / kg, about 10.5 mg / kg, about 10.6 mg / kg, about 10.7 mg / kg, about 10.8 mg / kg, about 10.9 mg / kg, about 11 mg / kg kg, about 11.1 mg / kg, about 11.2 mg / kg, about 11.3 mg / kg, about 11.4 mg / kg, about 11.5 mg / kg, about 11.6 mg / kg, about 11.7 mg / kg, about 11.8 mg / kg, about 11.9 mg / kg, about 12 mg / kg, about 12.1 mg / kg, about 12.2 mg / kg, about 12.3 mg / kg, about 12.4 mg / kg, about 12.5 mg / kg, about 12.6 mg / kg , About 12.7 mg / kg, about 12.8 mg / kg, about 12.9 mg / kg, about 13 mg / kg, about 13.1 mg / kg, about 13.2 mg / kg, about 13.3 mg / kg, about 13.4 mg / kg, about 13.5 mg / kg, about 13.6 mg / kg, about 13.7 mg / kg, about 13.8 mg / kg, about 13.9 mg / kg, about 14 mg / kg, about 14.1 mg / kg, about 14.2 mg / kg, about 14.3 mg / kg, about 14.4 mg / kg, about 14.5 mg / kg, about 14.6 mg / kg, about 14.7 mg / kg, about 14.8 mg / kg, about 14.9 mg / kg, about 15 mg / kg, about 15.1 mg / kg , About 15.2 mg / kg, about 15.3 mg / kg, about 15.4 mg / kg, about 15.5 mg / kg, about 15.6 mg / kg, about 15.7 mg / kg, about 15.8 mg / kg, about 15.9 mg / kg, about 16 mg / kg, about 16.1 mg / kg, about 16.2 mg / kg, about 16.3 mg / kg, about 16.4 mg / kg, about 16.5 mg / kg, about 16.6 mg / kg, about 16.7 mg / kg, about 16.8 mg / kg, about 16.9 mg / kg, about 17 mg / kg, about 17.1 mg / kg, about 17.2 mg / kg, about 17.3 mg / kg, about 17.4 mg / kg, about 17.5 mg / kg, about 17.6 mg / kg , About 17.7 mg / kg, about 17.8 mg / kg, about 17.9 mg / kg, about 18 mg / kg, about 18.1 mg / kg, About 18.2 mg / kg, about 18.3 mg / kg, about 18.4 mg / kg, about 18.5 mg / kg, about 18.6 mg / kg, about 18.7 mg / kg, about 18.8 mg / kg, about 18.9 mg / kg, about 19 mg / kg, about 19.1 mg / kg, about 19.2 mg / kg, about 19.3 mg / kg, about 19.4 mg / kg, about 19.5 mg / kg, about 19.6 mg / kg, about 19.7 mg / kg, about 19.8 mg / kg kg, about 19.9 mg / kg, or about 20 mg / kg. In some cases, a therapeutically effective amount or dose is encompassed to include a dose of about 0.1 mg / kg to about 2.0 mg / kg.

The role of ERFE in regulating iron metabolism is to regulate the content of hepcidin which directly regulates iron content. Increased ERFE activity results in a decrease in hepcidin content, which results in an increase in iron content. In contrast, reduced ERFE activity results in an increase in hepcidin content, which results in a decrease in iron content. Therefore, antibodies that increase ERFE content or activity increase iron content, and antibodies that decrease ERFE content or activity decrease iron content.

The methods of treatment herein include one or more administrations of the ERFE antibodies at the doses disclosed herein. In some embodiments, the method comprises a single administration of an ERFE antibody. In some embodiments, the method comprises two administrations of an ERFE antibody. In some embodiments, the method comprises three administrations of an ERFE antibody. In some embodiments, the method comprises four administrations of ERFE antibodies. In some embodiments, the method comprises five administrations of ERFE antibodies. In some embodiments, the method comprises six administrations of ERFE antibodies. In some embodiments, one or more administrations of the ERFE antibody are administered daily. In some embodiments, one or more administrations of the ERFE antibody are administered weekly. In some embodiments, one or more administrations of the ERFE antibody are administered every two weeks. In some embodiments, one or more administrations of the ERFE antibody are administered monthly. In some embodiments, one or more administrations of the ERFE antibody are administered every three months. In some embodiments, one or more administrations of the ERFE antibody are administered every six months. In some embodiments, one or more administrations of the ERFE antibody are administered annually.

The antibodies disclosed herein inhibit ERFE activity and increase hepcidin content, thereby reducing iron content. In some embodiments, the antibodies herein increase the hepcidin content by about 10%. In some embodiments, the antibodies herein increase the hepcidin content by about 15%. In some embodiments, the antibodies herein increase the hepcidin content by about 20%. In some embodiments, the antibodies herein increase the hepcidin content by about 25%. In some embodiments, the antibodies herein increase the hepcidin content by about 30%. In some embodiments, the antibodies herein increase the hepcidin content by about 35%. In some embodiments, the antibodies herein increase the hepcidin content by about 40%. In some embodiments, the antibodies herein increase the hepcidin content by about 45%. In some embodiments, the antibodies herein increase the hepcidin content by about 50%. In some embodiments, the antibodies herein increase the hepcidin content by about 55%. In some embodiments, the antibodies herein increase the hepcidin content by about 60%. In some embodiments, the antibodies herein increase the hepcidin content by about 65%. In some embodiments, the antibodies herein increase the hepcidin content by about 70%. In some embodiments, the antibodies herein increase the hepcidin content by about 75%. In some embodiments, the antibodies herein increase the hepcidin content by about 80%. In some embodiments, the antibodies herein increase the hepcidin content by about 85%. In some embodiments, the antibodies herein increase the hepcidin content by about 90%. In some embodiments, the antibodies herein increase the hepcidin content by about 95%. In some embodiments, the antibodies herein increase the hepcidin content by about 100%. In some embodiments, the antibodies herein increase the hepcidin content from about 10% to about 100%. In some embodiments, the antibodies herein increase hepcidin content by at least about 10%. In some embodiments, the antibodies herein increase the hepcidin content by up to about 100%. In some embodiments, the antibodies herein increase the hepcidin content by about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, and about 10% To about 60%, about 10% to about 70%, about 10% to about 80%, about 10% to about 90%, about 10% to about 100%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 90%, about 20% to about 100% About 30% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80%, about 30% to about 90%, about 30% to about 100%, about 40% to about 50%, about 40% to about 60%, about 40% to about 70%, about 40% to about 80%, about 40% to about 90%, about 40% To about 100%, about 50% to about 60%, about 50% to about 70%, about 50% to about 80%, about 50% to about 90%, about 50% to about 100%, about 60% to about 70%, about 60% to about 80%, about 60% to about 90%, about 60% to about 100%, about 70% to about 80%, about 70% to about 90%, about 70% to about 100% About 80% to about 90%, about 80% to about 100%, or about 90% to about 100%.

The antibodies disclosed herein inhibit ERFE activity and increase hepcidin content, thereby reducing iron content. In some embodiments, the antibodies herein reduce the iron content by about 5%. In some embodiments, the antibodies herein reduce the iron content by about 10%. In some embodiments, the antibodies herein reduce the iron content by about 15%. In some embodiments, the antibodies herein reduce the iron content by about 20%. In some embodiments, the antibodies herein reduce the iron content by about 25%. In some embodiments, the antibodies herein reduce the iron content by about 30%. In some embodiments, the antibodies herein reduce iron content by about 35%. In some embodiments, the antibodies herein reduce the iron content by about 40%. In some embodiments, the antibodies herein reduce the iron content by about 45%. In some embodiments, the antibodies herein reduce the iron content by about 50%. In some embodiments, the antibodies herein reduce the iron content from about 5% to about 50%. In some embodiments, the antibodies herein reduce iron content by at least about 5%. In some embodiments, the antibodies herein reduce the iron content by up to about 50%. In some embodiments, the antibodies herein reduce iron content by about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 5% to about 35%, about 5% to about 40%, about 5% to about 45%, about 5% to about 50%, about 10% to about 15%, about 10% to about 20% About 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 15% to approximately 20%, approximately 15% to approximately 25%, approximately 15% to approximately 30%, approximately 15% to approximately 35%, approximately 15% to approximately 40%, approximately 15% to approximately 45%, approximately 15% To about 50%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 30% to about 35% About 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 40% to about 45%, about 40% to about 50%, or about 45% to about 50%. In some embodiments, the antibodies herein reduce iron content by about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50%.
ERFE antibody composition

Also disclosed herein are compositions comprising an ERFE antibody and at least one buffer or excipient.

In some embodiments, excipients used with the compositions disclosed herein include maleic acid, tartaric acid, lactic acid, citric acid, acetic acid, sodium bicarbonate, sodium phosphate, histamine, glycine, sodium chloride , Potassium chloride, calcium chloride, zinc chloride, water, dextrose, N-methylpyrrolidone, dimethylarsine, N, N-dimethylacetamide, ethanol, propylene glycol, polyethylene glycol Alcohol, diethylene glycol monoethyl ether and surfactant polyoxyethylene-sorbitan monooleate. In some embodiments, the composition further comprises a carrier.

In some embodiments, the composition further comprises an additional therapeutic agent. In some embodiments, the additional therapeutic agent treats the symptoms of a disease or disorder of iron metabolism. In some embodiments, additional therapeutic agents increase the effectiveness of ERFE activity modulators. In some embodiments, the composition further comprises iron. In some embodiments, the composition further comprises erythropoietin.

In some embodiments, the pharmaceutical formulation is made compatible with a particular local, regional or systemic administration or delivery route. Thus, a pharmaceutical formulation includes a carrier, diluent or excipient suitable for administration by a particular route. Specific non-limiting examples of routes of administration of the compositions herein are parenteral, for example, intravenous, intraarterial, intradermal, intramuscular, subcutaneous, intrapleural, transdermal (topical), transmucosal, intracranial, Intraspinal, intraocular, rectal, oral (digestive), mucosal administration and any other formulation suitable for a treatment method or administration regimen.

In some embodiments, solutions or suspensions for parenteral administration include: sterile diluents, such as water for injection, saline solution, non-volatile oil, polyethylene glycol, glycerol, propylene glycol, or other synthetic solvents; antibacterial agents, Such as benzyl alcohol or methyl paraben; antioxidants such as ascorbic acid or sodium bisulfate; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetate, citrate or phosphate; and for regulating tonicity Reagents, such as sodium chloride or dextrose. In some embodiments, the pH is adjusted with an acid or a base, such as hydrochloric acid or sodium hydroxide.

Pharmaceutical formulations for injection include sterile aqueous solutions (if water-soluble) or dispersions and sterile powders for the temporary preparation of sterile injectable solutions or dispersions. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL ™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In some embodiments, the carrier is a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like) or a suitable mixture thereof. In some embodiments, for example, by using a coating (such as lecithin), in the case of a dispersion, by maintaining a desired particle size, and by using a surfactant to maintain fluidity. Antibacterial and antifungal agents include, for example, parabens, chlorobutanol, phenol, ascorbic acid, and thimerosal. In some embodiments, an isotonic agent, such as a sugar; a polyalcohol, such as mannitol or sorbitol; or sodium chloride, is included in the composition. In some cases, agents that delay absorption are also included. In some embodiments, for example, aluminum monostearate or gelatin prolongs the absorption of injectable compositions.

In some embodiments, a sterile injectable formulation is prepared by incorporating the required amount of the active composition with one or a combination of the above ingredients in a suitable solvent. Generally, dispersions are prepared by incorporating the active composition into a sterile vehicle that contains a basic dispersion matrix and any other ingredients. In the case of sterile powders for the preparation of sterile injectable solutions, the methods of preparation include, for example, vacuum drying and freeze drying, which produces a powder with the active ingredient plus any additional desired ingredients from its previously prepared solution.

For transmucosal or transdermal administration, penetrants suitable for penetrating the barrier are used in the formulation. These penetrants are known in the art and include, for example, bile salts and fusidic acid derivatives of cleaners for transmucosal administration. In some embodiments, transmucosal administration is accomplished via the use of a nasal spray, an inhalation device (eg, aspirator), or a suppository. For transdermal administration, the active compound is formulated as an ointment, ointment, gel, cream, or patch.

In some embodiments, pharmaceutical formulations are prepared using a vehicle that prevents rapid elimination from the body (such as a controlled release formulation or a time delay material, such as glyceryl monostearate or glyceryl stearate). In some embodiments, articles such as implants and microencapsulated delivery series are also used to deliver formulations to achieve local, regional or systemic delivery or controlled or sustained release.
definition

"ERFE" (also known as red iron-rich hormone), myonectin, complement C1q tumor necrosis factor-related protein 15 and member B with sequence similarity 132 member B generally refers to the ERFE protein encoded by the ERFE locus. Red iron-rich hormone or ERFE is an iron-regulating hormone used as a red blood cell regulator after bleeding. ERFE is produced by red blood cells after blood loss and mediates the suppression of hepcidin (HAMP) expression in the liver, thereby promoting increased iron absorption and mobilization from the repository. Generally, unless otherwise indicated, as used herein, ERFE refers to, for example, by listing ERFE genes, ERFE transcripts, proteins of ERFE antibodies, or recognizable fragments thereof. A fragment of ERFE refers to any set of contiguous residues of ERFE that uniquely or recognizably maps to a polypeptide sequence. ERFE is also occasionally informally referred to herein as a locus or gene encoding an ERFE protein.

As used herein, "antibody" refers to a glycoprotein that exhibits binding specificity to a specific antigen. Antibodies often include variable and constant domains in each of the heavy and light chains. Therefore, most antibodies have a heavy chain variable domain (VH) and a light chain variable domain (VL), which together form part of an antibody that binds to an antigen. Within each variable domain are three complementary determining regions (CDRs) that form a loop in the heavy chain variable domain (VH) and light chain variable domain (VL) that contact the surface of the antigen. Antibodies herein also include "antigen-binding portions" or fragments of antibodies capable of binding to an antigen.

As used herein, a "chimeric" antisystem is an antibody in which a portion of the heavy and / or light chain is the same or homologous to the corresponding sequence of an antibody derived from a particular species or a particular antibody class or subclass, and the (etc.) chain The remainder is identical or homologous to the corresponding sequence of an antibody derived from another species or another antibody class or subclass; and fragments of such antibodies, as long as they exhibit the desired biological activity (see, for example, Morrison et al., Proc. Natl. Acad. Sci. USA 81: 6851-6855 (1984)). A "humanized antibody" herein refers to a chimeric antibody in which the human sequence has been substituted in the antibody sequence.

A "neutralizing antibody" as used herein is an antibody capable of inhibiting a target protein. In some embodiments, the anti-ERFE neutralizing antibody reduces circulating ERFE content. In some embodiments, an anti-ERFE neutralizing antibody reduces ERFE activity. In some embodiments, the anti-ERFE neutralizing antibody inhibits or prevents ERFE from binding to the receptor.

As used herein, "iron metabolism disorders" and "iron metabolism disorders" refer to diseases and disorders that affect serum iron content or the ability of an individual to maintain a healthy iron content. Iron metabolism diseases and disorders herein include diseases and disorders in which the individual's iron content is lower than normal (such as anemia or iron deficiency) and diseases and disorders in which the individual's iron content is higher than normal (such as iron overload or hemochromatosis).

The terms "recipient", "individual", "subject", "host" and "patient" are used interchangeably herein and in some cases refer to any mammal that desires a diagnosis, treatment, or therapy Individuals, specifically humans. "Mammalian" for therapeutic purposes means any animal classified as a mammal, including humans, domestic and farm animals and laboratory animals, zoo animals, sport animals or pets (e.g. dogs, horses, cats, cattle, sheep , Goat, pig, mouse, rat, rabbit, guinea pig, monkey, etc.). In some embodiments, the mammal is human.

As used herein, the term "treatment," and the like, refers in some cases to the administration of drugs or procedures for the purpose of obtaining an effect. The effect may be prophylactic in terms of completely or partially preventing the disease or its symptoms, and / or the effect may be therapeutic in terms of achieving partial or complete cure of the disease and / or symptoms of the disease. "Treatment" as used herein may include treatment of iron metabolic diseases or conditions in mammals, and specifically humans, and includes: (a) preventing diseases or symptoms of a disease that may be predisposed to the disease but has not yet been diagnosed with the disease ( Examples include those that can be associated with or caused by a primary disease); (b) inhibit the disease, that is, stop its development; and (c) reduce the disease, that is, cause the regression of the disease. Treatment can refer to treating or improving or preventing any marker of success in cancer, including any objective or subjective parameters, such as reduction; alleviation; reduction of symptoms or making the disease condition more tolerant to the patient; slowing or decreasing the rate of degeneration; or The final point is less debilitating. Treatment or amelioration of symptoms is based on one or more objective or subjective parameters; including the results of a physician examination. Thus, the term "treatment" includes administration of a compound or agent of the invention to prevent or delay, mitigate or stop or inhibit the development of symptoms or conditions associated with cancer or other diseases. The term "therapeutic effect" refers to reducing, eliminating or preventing an individual's disease, disease symptoms, or side effects of the disease.

The terms "pharmaceutically acceptable", "physiologically tolerable" and their grammatical variations are used interchangeably when referring to compositions, carriers, diluents, and reagents, and in some cases indicate that a substance can be administered to humans It does not produce undesired physiological effects to the extent that administration of the composition will be prohibited.

A "therapeutically effective amount" means in some cases an amount sufficient to effect treatment of a disease when administered to an individual for the treatment of the disease.

Unless the context clearly indicates otherwise, as used herein, the singular forms "a" and "the" include plural referents. Thus, for example, reference to "one antibody" includes a plurality of antibodies, and in some embodiments reference to "one antibody" includes multiple antibodies, and so on.

Unless the context clearly indicates otherwise, all numerical values or numerical ranges, as used herein, include integers within such ranges or encompassing those ranges, and values or fractions of integers within or between ranges. Thus, for example, reference to the range of 90-100% includes 91%, 92%, 93%, 94%, 95%, 95%, 97%, etc., and 91.1%, 91.2%, 91.3%, 91.4%, 91.5%, etc., 92.1%, 92.2%, 92.3%, 92.4%, 92.5%, etc. In another example, the range of 1-5,000 times includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 , 19, 20 times, etc., and 1.1, 1.2, 1.3, 1.4, 1.5 times, etc., 2.1, 2.2, 2.3, 2.4, 2.5 times, etc.

As used herein, a "about" number refers to a range that includes a number and is in the range of less than 10% to more than 10% of the number. A range of "about" means 10% below the lower limit of the range and extending to 10% above the upper limit of the range.
Examples

The following examples are given for the purpose of illustrating various embodiments of the invention and are not intended to limit the invention in any way. The examples of the invention and the methods described herein currently represent preferred embodiments, are exemplary, and are not intended to limit the scope of the invention. Those skilled in the art will understand the variations therein and other uses covered by the spirit of the invention as defined by the scope of the patent application.
Example 1 : Anti- ERFE Monoclonal Antibody Generation and Sequencing

Following a procedure known to those skilled in the art, mice are immunized with Fc-mERFE 24-340 using a multisite-modified rapid immunization (RIMMS) protocol. After establishing a high titer response to the immunogen, lymph node B cells were electrofused to mouse myeloma cells. The resulting hybridomas were inoculated into soft agar, and individual colonies were picked and grown in 96-well plates. Supernatants from approximately 2400 wells were screened for mERFE reactivity. Unrelated Fc-fusion proteins are used to eliminate binding agents to the human Fc portion of the immunogen. To support the screening and characterization of the resulting hybridomas, multiple mouse and human ERFE recombinant proteins containing different putative functional domains of the protein were generated in the HEK293-Freestyle system. Of the 2400 hybridoma lines that were initially screened, 65 were identified as positive for binding to Fc-mERFE 24-340 (immunogen) by ELISA and negative for irrelevant Fc-fusion proteins used for rescreening . After follow-up of these 65 pure lines, it was confirmed that 29 Fc-mERFE 24-340 (immunogens) and HIS-Flag mERFE 24-340 (confirmed specific binding to mERFE) protein). Of the 29 pure lines, 19 were also found to bind HIS-Flag hERFE by ELISA with a> 10-fold signal relative to the background. The 19 mouse / human cross-reactive binding agents were selected for functional characterization.

Three monoclonal antibodies showing specific binding to ERFE were isolated and cloned using conventional methods. Three antibodies were sequenced to determine the sequence of the heavy chain variable domain (VH), the light chain variable domain (VL), and the complementarity determining regions (CDR) of the heavy and light chains. The sequences obtained are summarized in Table 1.
Example 2 : Functional antibody screening

Nineteen mouse / human ERFE-reactive antibody pure lines identified in the hybridoma screen were analyzed in Hep3B hepcidin mRNA ( HAMP ) cell analysis (Figure 1). The ability of hybridoma supernatants containing ERFE-specific antibodies to inhibit ERFE-mediated inhibition of hepcidin content was tested by neutralizing the effect of Fc-mERFE 24-340 protein. To determine neutralization, 500 ng / ml Fc-mERFE 24-340 was pre-incubated with hybridoma supernatant (1: 5 dilution) for 30 minutes. The mixture was added to Hep3B cells for 15 hours, after which the relative HAMP expression value was determined. Two hybridoma pure lines were identified, which completely blocked the inhibitory effect of Fc-mERFE 24-340 on HAMP performance. Since this analysis was performed using hybridoma supernatants that have not been normalized for antibody concentration, two additional pure lines showing low / medium inhibitory activity relative to the control hybridoma matrix were also selected for follow-up, considering Low activity may be due to the potential for lower antibody concentrations in the sample.
Example 3 : Identification of Primary Monoclonal Antibodies

In order to follow up the data from the hybridoma supernatants, purified antibodies from the hybridomas were confirmed for binding by ELISA, and functional activity was determined in a cell Hep3B hepcidin mRNA ( HAMP ) inhibition assay (Figure 2A and Figure 2B). 4F7, 10D9, and 9E3 antibodies were pre-incubated with 1 μg / ml HIS-Flag hERFE 28-354, added to Hep3B cells, and the relative HAMP performance was determined after 6 hours of incubation. Pure 4F7, 10D9, and 9E3 purified antibodies showed dose-dependent inhibition of ERFE-mediated HAMP inhibition.
Example 4 : Anti- ERFE monoclonal antibody binding

Monovalent human ERFE was used to determine the binding affinity of individual antibodies by ForteBio Octet Bio-Layer interference measurement analysis. Briefly, αERFE Ab was captured on Dip and Readä anti-mouse IgG Fc Capture (AMC) Biosensors (ForteBio) in PBS + 0.1% BSA + 0.02% Tween-20 (pH 7.2) in assay buffer at room temperature. (30 μg / ml). The sensor was washed in analysis buffer and then incubated with purified monovalent human ERFE construct (100 nM) in analysis buffer for 5 minutes in a 2-fold dilution series to determine the association kinetics of the antibody and protein antigen. The sensor was then incubated in analysis buffer for 10 minutes to determine the dissociation kinetics. The kinetic parameters were calculated using a ForteBio analysis kit 8.0 using a 1: 1 model. The data are summarized in Table 2.
Example 5 : Functional dose response in vitro

Three pure ERFE-reactive antibody lines were analyzed in Hep3B hepcidin mRNA ( HAMP ) cell analysis. The ability of ERFE-specific antibodies to inhibit ERFE-mediated inhibition of hepcidin content was tested by neutralizing the effect of FlagHis-hERFE 28-354 protein. To determine neutralization, 1 ug / ml FlagHis-hERFE 28-354 was pre-incubated with antibodies at various antibody-to-antigen ratios for 30 minutes. The mixture was added to Hep3B cells for 6 hours, after which the relative HAMP expression value was determined. The data for this experiment are provided in Table 3 below.
Example 6 : In vivo treatment of animal model β -thalassemia

The in vivo potency of ERFE antibody pure lines was determined in a mouse model of β-thalassemia.

Heterozygous mice with genotype B6.129P2- Hbb-b1 ^tm1Unc Hbb-b2 ^tm1Unc / J (also known as Th3 / + mice) show the typical characteristics of severe thalassemia and are considered to be β-thalassemia Mouse model. To evaluate the in vivo efficacy of ERFE mAb, Th3 / + mice (3-4 weeks of age) were treated with ERFE antibodies once a week at a dose of 10 mg / kg for three weeks. At the end of the study, hepcidin and iron content in serum and liver were analyzed.

Compared with control mAb, anti-ERER antibodies effectively neutralize ERFE-mediated hepcidin inhibition, resulting in increased hepcidin performance in mRNA ( Hamp ) and protein levels, and most importantly, significantly reduced Iron load in the liver of these animals. These data are provided in Figures 3A, 3B, 4A, 4B, 5A and 5B. Figures 3A and 3B show changes in serum hepcidin content treated with anti-ERFE antibodies compared to controls. Figure 3A shows that the serum hepcidin content of the 4F7 antibody was increased compared to the control and the hepcidin content of the 10D9 antibody was not changed compared to the control. Figure 3B shows that the serum hepcidin content of the 9E3 antibody was increased compared to the control. Figures 4A and 4B show an increase in hepcidin mRNA treated with anti-ERFE antibodies compared to controls. Figure 4A shows the increase in hepcidin mRNA of the 4F7 and 10D9 antibodies compared to the control. Figure 4B shows that hepcidin mRNA of the 9E3 antibody is increased compared to the control. Figures 5A and 5B show reduced liver iron content in mice treated with anti-ERFE antibodies compared to controls. Figure 5A shows liver iron reduction in mice treated with 4F7 and 10D9 antibodies compared to controls. Figure 5B shows a decrease in liver iron content in mice treated with the 9E3 antibody compared to controls.

This example shows that antibodies 4F7, 10D9 and 9E3 show therapeutic efficacy in a mouse model of β-thalassemia.

Although preferred embodiments of the invention have been shown and described herein, it will be apparent to those skilled in the art that these embodiments are provided by way of example only. Those skilled in the art will now contemplate various changes, modifications, and substitutions without departing from the invention. It should be understood that various alternative forms of the embodiments described herein may be employed. The following patent application scopes are intended to define the scope of the invention and thereby cover the methods and structures within the scope of these patent applications and their equivalent forms.

The features and advantages of the present invention can be better understood with reference to the illustrative embodiments illustrating the principles of the present invention and the following drawings, in which:

Figure 1 shows screening of functional anti-ERFE antibodies by inhibition analysis of anti-ERFE hybridomas.

Figure 2A shows the in vitro functional dose response of 4F7 and 10D9 in inhibiting ERFE-mediated HAMP inhibition.

Figure 2B shows the in vitro functional dose response of 4F7 and 9E3 in inhibiting ERFE-mediated HAMP inhibition.

Figure 3A shows the in vivo increase in serum hepcidin in mice treated with 4F7 and 10D9 anti-ERFE antibodies.

Figure 3B shows the in vivo increase in serum hepcidin in mice treated with 9E3 anti-ERFE antibodies.

Figure 4A shows in vivo increase of hepcidin mRNA in mice treated with 4F7 and 10D9 anti-ERFE antibodies.

Figure 4B shows the in vivo increase of hepcidin mRNA in mice treated with 9E3 anti-ERFE antibody.

Figure 5A shows in vivo reduction of liver iron content treated with 4F7 and 10D9 anti-ERFE antibodies.

Figure 5B shows in vivo reduction of liver iron content treated with 9E3 anti-ERFE antibody.

Claims (246)

A monoclonal antibody or an antigen-binding fragment thereof comprising an amino acid sequence comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL). The monoclonal antibody of claim 1, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an antibody having an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 having at least 90 Light chain variable domain (VL) of amino acid sequence with% identity. The monoclonal antibody of claim 1 or 2, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an antibody comprising an amino acid sequence as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 having Light chain variable domain (VL) of an amino acid sequence that is at least 95% identical. The monoclonal antibody of any one of claims 1 to 3, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The light chain variable domain (VL) of the amino acid sequence has at least 99% identity. The monoclonal antibody of any one of claims 1 to 4, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of amino acid sequences with 100% amino acid sequence identity. The monoclonal antibody of any one of claims 1 to 5, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy-chain variable domain (VH) of the amino acid sequence has at least 80% identity. The monoclonal antibody according to any one of claims 1 to 6, wherein the monoclonal antibody or an antigen-binding fragment thereof, wherein the monoclonal antibody or the antigen-binding fragment thereof comprises a antibody comprising SEQ ID NO: 20, SEQ ID NO: The amino acid sequence of 22 or SEQ ID NO: 24 has a heavy chain variable domain (VH) of an amino acid sequence that is at least 90% identical. The monoclonal antibody of any one of claims 1 to 7, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy-chain variable domain (VH) of the amino acid sequence has at least 95% identity. The monoclonal antibody of any one of claims 1 to 8, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The amino acid sequence has a heavy chain variable domain (VH) of an amino acid sequence that is at least 99% identical. The monoclonal antibody of any one of claims 1 to 9, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence has 100% identity. The monoclonal antibody of any one of claims 1 to 10, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises a light chain variable structure comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 19 Domain (VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 20. The monoclonal antibody of any one of claims 1 to 10, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable structure comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 21 Domain (VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 22. The monoclonal antibody of any one of claims 1 to 10, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises a light chain variable structure comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 23 Domain (VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 24. The monoclonal antibody of any one of claims 1 to 13, wherein the monoclonal antibody or an antigen-binding fragment thereof specifically binds to an ERFE protein. The monoclonal antibody of any one of claims 1 to 14, wherein the monoclonal antibody or an antigen-binding fragment thereof is selected from the group consisting of whole immunoglobulin, scFv, Fab, F (ab ') ₂ or disulfide-linked Fv . The monoclonal antibody of any one of claims 1 to 15, wherein the monoclonal antibody or an antigen-binding fragment thereof is IgG or IgM. The monoclonal antibody of any one of claims 1 to 16, wherein the monoclonal antibody or a fragment thereof is humanized or chimeric. A monoclonal antibody or an antigen-binding fragment thereof comprising an amino acid sequence comprising at least 80% identity to an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 Heavy chain variable domain (VH). The monoclonal antibody of claim 18, wherein the monoclonal antibody or antigen-binding fragment thereof comprises an antibody having an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 having at least 90 Heavy chain variable domain (VH) of amino acid sequence with% identity. The monoclonal antibody of claim 18 or 19, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an antibody comprising an amino acid sequence as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24. Heavy chain variable domain (VH) of an amino acid sequence that is at least 95% identical. The monoclonal antibody of any one of claims 18 to 20, wherein the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The amino acid sequence has a heavy chain variable domain (VH) of an amino acid sequence that is at least 99% identical. The monoclonal antibody of any one of claims 18 to 21, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of the amino acid sequence has 100% identity. The monoclonal antibody of any one of claims 18 to 22, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The light chain variable domain (VL) of the amino acid sequence has at least 80% identity. The monoclonal antibody of any one of claims 18 to 23, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The light chain variable domain (VL) of the amino acid sequence has at least 90% identity. The monoclonal antibody of any one of claims 18 to 24, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The light chain variable domain (VL) of the amino acid sequence has at least 95% identity. The monoclonal antibody of any one of claims 18 to 25, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The light chain variable domain (VL) of the amino acid sequence has at least 99% identity. The monoclonal antibody of any one of claims 18 to 26, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) of amino acid sequences with 100% amino acid sequence identity. The monoclonal antibody of any one of claims 18 to 27, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises a heavy chain variable structure comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 20 Domain (VH) and a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 19. The monoclonal antibody of any one of claims 18 to 27, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable structure comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 22 Domain (VH) and a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 21. The monoclonal antibody of any one of claims 18 to 27, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable structure comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 24 Domain (VH) and a light chain variable domain (VL) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 23. The monoclonal antibody of any one of claims 18 to 30, wherein the monoclonal antibody or an antigen-binding fragment thereof specifically binds to an ERFE protein. The monoclonal antibody of any one of claims 18 to 31, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from the group consisting of whole immunoglobulin, scFv, Fab, F (ab ') ₂ or disulfide-linked Fv . The monoclonal antibody of any one of claims 18 to 32, wherein the monoclonal antibody or an antigen-binding fragment thereof is IgG or IgM. The monoclonal antibody of any one of claims 18 to 33, wherein the monoclonal antibody or a fragment thereof is humanized or chimeric. A monoclonal antibody or an antigen-binding fragment thereof, comprising a light chain having at least 80% identity to at least one of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15 Complementarity determining region (CDR) sequences. The monoclonal antibody according to claim 35, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amino acid sequence having at least one of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15 Light chain complementarity determining region (CDR) sequences that are at least 90% identical. The monoclonal antibody of claim 35 or 36, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least one of the amino acid sequences as described in SEQ ID NOs: 1-3, 7-9, and 13-15 This has a light chain complementarity determining region (CDR) sequence that is at least 95% identical. The monoclonal antibody of any one of claims 35 to 37, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amino acid sequence as described in SEQ ID NOs: 1-3, 7-9, and 13-15 At least one of them has a light chain complementarity determining region (CDR) sequence that is at least 99% identical. The monoclonal antibody of any one of claims 35 to 38, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amino acid sequence as described in SEQ ID NOs: 1-3, 7-9, and 13-15 At least one of them has a light chain complementarity determining region (CDR) sequence that is 100% identical. The monoclonal antibody of any one of claims 35 to 39, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amino acid sequence as described in SEQ ID NOs: 4-6, 10-12, and 16-18 At least one of them has a heavy chain complementarity determining region (CDR) sequence that is at least 80% identical. The monoclonal antibody of any one of claims 35 to 40, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Heavy chain complementarity determining region (CDR) sequences with at least 90% identity. The monoclonal antibody of any one of claims 35 to 41, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Heavy chain complementarity determining region (CDR) sequences with at least 95% identity. The monoclonal antibody of any one of claims 35 to 42, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Heavy chain complementarity determining region (CDR) sequences with at least 99% identity. The monoclonal antibody of any one of claims 35 to 43, wherein the monoclonal antibody or antigen-binding fragment thereof comprises an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Heavy chain complementarity determining region (CDR) sequences with 100% identity. The monoclonal antibody of any one of claims 35 to 44, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least one of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 13 80% identical light chain complementarity determining region 1 (CDR1) sequences, a light chain complementarity determining region having at least 80% identity with one of SEQ ID NO: 2, SEQ ID NO: 8 or SEQ ID NO: 14 2 (CDR2) sequence, a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity to one of SEQ ID NO: 3, SEQ ID NO: 9 or SEQ ID NO: 15, and SEQ ID NO : 4. One of SEQ ID NO: 10 or SEQ ID NO: 16 has a heavy chain complementarity determining region 1 (CDR1) sequence that is at least 80% identical to SEQ ID NO: 5, SEQ ID NO: 11 or SEQ One of ID NO: 17 has a heavy chain complementarity determining region 2 (CDR2) sequence that is at least 80% identical and has at least 80% identity to one of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 13 80% identical heavy chain complementarity determining region 3 (CDR3) sequences. The monoclonal antibody of any one of claims 35 to 45, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 1, A light chain complementarity determining region 2 (CDR2) sequence with at least 80% identity with SEQ ID NO: 2 and a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 3. The monoclonal antibody of claim 46, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 31. The monoclonal antibody of claim 46, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 32. The monoclonal antibody of claim 46, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 33. The monoclonal antibody of claim 46, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 34. The monoclonal antibody of any one of claims 35 to 45, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 7, A light chain complementarity determining region 2 (CDR2) sequence with at least 80% identity with SEQ ID NO: 8 and a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 9. The monoclonal antibody of any one of claims 35 to 45, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 13, A light chain complementarity determining region 2 (CDR2) sequence with at least 80% identity with SEQ ID NO: 14 and a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 15. The monoclonal antibody of claim 52, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 43. The monoclonal antibody of claim 52, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 44. The monoclonal antibody of claim 52, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 45. The monoclonal antibody of claim 52, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 46. The monoclonal antibody of any one of claims 35 to 56, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 4, A heavy chain complementarity determining region 2 (CDR2) sequence with at least 80% identity with SEQ ID NO: 5 and a heavy chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 6. The monoclonal antibody of claim 57, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 35. The monoclonal antibody of claim 57, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 36. The monoclonal antibody of claim 57, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 37. The monoclonal antibody of claim 57, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 38. The monoclonal antibody of any one of claims 35 to 56, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 10, A heavy chain complementarity determining region 2 (CDR2) sequence with at least 80% identity with SEQ ID NO: 11 and a heavy chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 12. The monoclonal antibody of claim 62, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 39. The monoclonal antibody of claim 62, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 40. The monoclonal antibody of claim 62, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 41. The monoclonal antibody of claim 62, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 42. The monoclonal antibody of any one of claims 35 to 56, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 16, A heavy chain complementarity determining region 2 (CDR2) sequence with at least 80% identity with SEQ ID NO: 17 and a heavy chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 18. The monoclonal antibody of claim 67, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 47. The monoclonal antibody of claim 67, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 48. The monoclonal antibody of claim 67, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 49. The monoclonal antibody of claim 67, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 50. The monoclonal antibody of claim 67, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 51. The monoclonal antibody of claim 67, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 52. The monoclonal antibody of claim 67, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 53. The monoclonal antibody of claim 67, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 54. The monoclonal antibody of any one of claims 35 to 75, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The light chain variable domain (VL) of the amino acid sequence has at least 80% identity. The monoclonal antibody of any one of claims 35 to 76, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy-chain variable domain (VH) of the amino acid sequence has at least 80% identity. The monoclonal antibody of any one of claims 35 to 77, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 Light chain variable domain (VL) having an amino acid sequence having at least 80% identity; and an amine comprising the amino acid sequence described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy-chain variable domain (VH) of the amino acid sequence has at least 80% identity. The monoclonal antibody of any one of claims 35 to 78, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 Heavy chain variable domain (VH) of an amino acid sequence having at least 80% identity; and comprising an amine as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The light chain variable domain (VL) of the amino acid sequence has at least 80% identity. The monoclonal antibody of any one of claims 35 to 79, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable structure comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 19 Domain (VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 20. The monoclonal antibody of any one of claims 35 to 79, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable structure comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 21 Domain (VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 22. The monoclonal antibody of any one of claims 35 to 79, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable structure comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 23 Domain (VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 24. The monoclonal antibody of any one of claims 35 to 82, wherein the monoclonal antibody or an antigen-binding fragment thereof specifically binds to an ERFE protein. The monoclonal antibody of any one of claims 35 to 83, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from the group consisting of a whole immunoglobulin, scFv, Fab, F (ab ') ₂ or disulfide-linked Fv . The monoclonal antibody of any one of claims 35 to 84, wherein the monoclonal antibody or an antigen-binding fragment thereof is IgG or IgM. The monoclonal antibody of any one of claims 35 to 85, wherein the monoclonal antibody or a fragment thereof is humanized or chimeric. A monoclonal antibody or an antigen-binding fragment thereof comprising a heavy chain having at least 80% identity to at least one of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18 Complementarity determining region (CDR) sequences. The monoclonal antibody of claim 87, wherein the monoclonal antibody or antigen-binding fragment comprises at least one amino acid sequence as described in SEQ ID NOs: 4-6, 10-12, and 16-18. 90% identical heavy chain complementarity determining region (CDR) sequences. The monoclonal antibody of claim 87 or 88, wherein the monoclonal antibody or antigen-binding fragment comprises at least one of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18 Heavy chain complementarity determining region (CDR) sequences with at least 95% identity. The monoclonal antibody of any one of claims 87 to 89, wherein the monoclonal antibody or antigen-binding fragment is included in the amino acid sequence as described in SEQ ID NOs: 4-6, 10-12, and 16-18 At least one of them has a heavy chain complementarity determining region (CDR) sequence that is at least 99% identical. The monoclonal antibody of any one of claims 87 to 90, wherein the monoclonal antibody or antigen-binding fragment is included in the amino acid sequence as described in SEQ ID NOs: 4-6, 10-12, and 16-18 At least one of them has a 100% identical heavy chain complementarity determining region (CDR) sequence. The monoclonal antibody of any one of claims 87 to 91, wherein the monoclonal antibody or antigen-binding fragment is included in the amino acid sequence as described in SEQ ID NOs: 1-3, 7-9, and 13-15 At least one of them has a light chain complementarity determining region (CDR) sequence that is at least 80% identical. The monoclonal antibody of any one of claims 87 to 92, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Heavy chain complementarity determining region (CDR) sequences with at least 90% identity. The monoclonal antibody of any one of claims 87 to 93, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Heavy chain complementarity determining region (CDR) sequences with at least 95% identity. The monoclonal antibody of any one of claims 87 to 94, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Heavy chain complementarity determining region (CDR) sequences with at least 99% identity. The monoclonal antibody of any one of claims 87 to 95, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amino acid sequence as described in SEQ ID NO: 4-6, 10-12, or 16-18 Heavy chain complementarity determining region (CDR) sequences with 100% identity. The monoclonal antibody of any one of claims 87 to 96, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least one of SEQ ID NO: 4, SEQ ID NO: 10, or SEQ ID NO: 16 80% identical heavy chain complementarity determining region 1 (CDR1) sequence, a heavy chain complementarity determining region having at least 80% identity to one of SEQ ID NO: 5, SEQ ID NO: 11 or SEQ ID NO: 17 2 (CDR2) sequence, heavy chain complementarity determining region 3 (CDR3) sequence with at least 80% identity to one of SEQ ID NO: 1, SEQ ID NO: 7 or SEQ ID NO: 13, and SEQ ID NO : 1. One of SEQ ID NO: 7 or SEQ ID NO: 13 having at least 80% identity to the light chain complementarity determining region 1 (CDR1) sequence, which is identical to SEQ ID NO: 2, SEQ ID NO: 8 or SEQ One of ID NO: 14 has at least 80% identity to the light chain complementarity determining region 2 (CDR2) sequence and has at least 80% identity with one of SEQ ID NO: 3, SEQ ID NO: 9, or SEQ ID NO: 15 80% identical light chain complementarity determining region 3 (CDR3) sequences. The monoclonal antibody of any one of claims 87 to 97, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 4, A heavy chain complementarity determining region 2 (CDR2) sequence with at least 80% identity with SEQ ID NO: 5 and a heavy chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 6. The monoclonal antibody of claim 98, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 35. The monoclonal antibody of claim 98, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 36. The monoclonal antibody of claim 98, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 37. The monoclonal antibody of claim 98, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 38. The monoclonal antibody of any one of claims 87 to 97, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 10, A heavy chain complementarity determining region 2 (CDR2) sequence with at least 80% identity with SEQ ID NO: 11 and a heavy chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 12. The monoclonal antibody of claim 103, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 39. The monoclonal antibody of claim 103, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 40. The monoclonal antibody of claim 103, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 41. The monoclonal antibody of claim 103, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 42. The monoclonal antibody of any one of claims 87 to 97, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 16, A heavy chain complementarity determining region 2 (CDR2) sequence with at least 80% identity with SEQ ID NO: 17 and a heavy chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 18. The monoclonal antibody of claim 108, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 47. The monoclonal antibody of claim 108, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 48. The monoclonal antibody of claim 108, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 49. The monoclonal antibody of claim 108, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 50. The monoclonal antibody of claim 108, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 51. The monoclonal antibody of claim 108, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 52. The monoclonal antibody of claim 108, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 53. The monoclonal antibody of claim 108, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 54. The monoclonal antibody of any one of claims 87 to 116, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 1, A light chain complementarity determining region 2 (CDR2) sequence with at least 80% identity with SEQ ID NO: 2 and a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 3. The monoclonal antibody of claim 117, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 31. The monoclonal antibody of claim 117, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 32. The monoclonal antibody of claim 117, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 33. The monoclonal antibody of claim 117, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 34. The monoclonal antibody of any one of claims 87 to 116, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 7, A light chain complementarity determining region 2 (CDR2) sequence with at least 80% identity with SEQ ID NO: 8 and a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 9. The monoclonal antibody of any one of claims 87 to 116, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 13, A light chain complementarity determining region 2 (CDR2) sequence with at least 80% identity with SEQ ID NO: 14 and a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 15. The monoclonal antibody of claim 123, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 43. The monoclonal antibody of claim 123, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 44. The monoclonal antibody of claim 123, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 45. The monoclonal antibody of claim 123, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 46. The monoclonal antibody of any one of claims 87 to 127, wherein the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy-chain variable domain (VH) of the amino acid sequence has at least 80% identity. The monoclonal antibody of any one of claims 87 to 128, wherein the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The light chain variable domain (VL) of the amino acid sequence has at least 80% identity. The monoclonal antibody of any one of claims 87 to 129, wherein the monoclonal antibody or antigen-binding fragment thereof comprises an amine comprising the amine described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 Heavy chain variable domain (VH) of an amino acid sequence having at least 80% identity; and comprising an amine as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The light chain variable domain (VL) of the amino acid sequence has at least 80% identity. The monoclonal antibody of any one of claims 87 to 130, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable structure comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 19 Domain (VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 20. The monoclonal antibody of any one of claims 87 to 130, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable structure comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 21 Domain (VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 22. The monoclonal antibody of any one of claims 87 to 130, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable structure comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 23 Domain (VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 24. The monoclonal antibody of any one of claims 87 to 133, wherein the monoclonal antibody or an antigen-binding fragment thereof specifically binds to an ERFE protein. The monoclonal antibody of any one of claims 87 to 134, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from the group consisting of whole immunoglobulin, scFv, Fab, F (ab ') ₂ or disulfide-linked Fv . The monoclonal antibody of any one of claims 87 to 135, wherein the monoclonal antibody or an antigen-binding fragment thereof is IgG or IgM. The monoclonal antibody of any one of claims 87 to 136, wherein the monoclonal antibody or a fragment thereof is humanized or chimeric. A method of treating a disease or condition of iron metabolism in a subject in need thereof, comprising administering an effective amount of a monoclonal antibody such as any one of claims 1 to 137. A method of treating an iron metabolism disease or disorder in a subject in need thereof, comprising administering to the individual an effective amount of a monoclonal antibody to treat the iron metabolism disease or disorder, wherein the monoclonal antibody comprises a compound such as 3. At least one of the amino acid sequences described in 7-9 and 13-15 has a light chain complementarity determining region (CDR) sequence that is at least 80% identical. A method of treating an iron metabolism disease or disorder in an individual in need thereof, comprising administering to the individual an effective amount of a monoclonal antibody to treat the iron metabolism disease or disorder, wherein the monoclonal antibody comprises a compound such as SEQ ID NO: 6. At least one of the amino acid sequences described in 6, 10-12, and 16-18 has a heavy chain complementarity determining region (CDR) sequence that is at least 80% identical. The method of claim 139 or 140, wherein the monoclonal antibody comprises at least 80% of at least one of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15 Identical light chain complementarity determining region (CDR) sequences; and b) at least 80% identical to at least one of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18 Sexual heavy chain complementarity determining region (CDR) sequences. The method of any one of claims 139 to 141, wherein the monoclonal antibody comprises a) and at least two of the amino acid sequences according to SEQ ID NOs: 1-3, 7-9, and 13-15 A light chain complementarity determining region (CDR) sequence having at least 80% identity; and b) having at least two of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18 Heavy chain complementarity determining region (CDR) sequences that are at least 80% identical. The method of any one of claims 139 to 142, wherein the monoclonal antibody comprises a) having at least 90% identity to an amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 Sex light chain complementarity determining region (CDR) sequences; and b) heavy chain complementarity decisions having at least 90% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18 Region (CDR) sequence. The method of any one of claims 139 to 143, wherein the monoclonal antibody comprises a) having at least 95% identity to an amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 Sex light chain complementarity determining region (CDR) sequences; and b) heavy chain complementarity decisions that have at least 95% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18 Region (CDR) sequence. The method of any one of claims 139 to 144, wherein the monoclonal antibody comprises a) having at least 99% identity to an amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 Sex light chain complementarity determining region (CDR) sequences; and b) heavy chain complementarity decisions that have at least 99% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18 Region (CDR) sequence. The method of any one of claims 139 to 145, wherein the monoclonal antibody comprises a) 100% identity to an amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 Light chain complementarity determining region (CDR) sequence; and b) a heavy chain complementarity determining region having 100% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18 ( CDR) sequence. The method of any one of claims 139 to 146, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least 80% of one of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 13 Consistent light chain complementarity determining region 1 (CDR1) sequences, a light chain complementarity determining region 2 having at least 80% identity to one of SEQ ID NO: 2, SEQ ID NO: 8, or SEQ ID NO: 14 ( CDR2) sequence, a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity to one of SEQ ID NO: 3, SEQ ID NO: 9 or SEQ ID NO: 15, and SEQ ID NO: 4 , A heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with one of SEQ ID NO: 10, or SEQ ID NO: 16, and SEQ ID NO: 5, SEQ ID NO: 11, or SEQ ID NO : One of 17 has at least 80% identity to the heavy chain complementarity determining region 2 (CDR2) sequence and at least 80% to one of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 13 Consistent heavy chain complementarity determining region 3 (CDR3) sequences. The method of any one of claims 139 to 147, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 1, and ID NO: 2 has a light chain complementarity determining region 2 (CDR2) sequence with at least 80% identity and a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 3. The monoclonal antibody of claim 148, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 31. The monoclonal antibody of claim 148, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 32. The monoclonal antibody of claim 148, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 33. The monoclonal antibody of claim 148, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 34. The method of any one of claims 139 to 147, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 7, and a sequence ID NO: 8 has a light chain complementarity determining region 2 (CDR2) sequence with at least 80% identity and a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 9. The method of any one of claims 139 to 147, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 13, and ID NO: 14 has a light chain complementarity determining region 2 (CDR2) sequence with at least 80% identity and a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 15. The monoclonal antibody of claim 154, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 43. The monoclonal antibody of claim 154, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 44. The monoclonal antibody of claim 154, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 45. The monoclonal antibody of claim 154, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 46. The method of any one of claims 139 to 158, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 4, ID NO: 5 has a heavy chain complementarity determining region 2 (CDR2) sequence with at least 80% identity and a heavy chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 6. The monoclonal antibody of claim 159, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 35. The monoclonal antibody of claim 159, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 36. The monoclonal antibody of claim 159, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 37. The monoclonal antibody of claim 159, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 38. The method of any one of claims 139 to 158, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 10, and ID NO: 11 has a heavy chain complementarity determining region 2 (CDR2) sequence with at least 80% identity and a heavy chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 12. The monoclonal antibody of claim 164, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 39. The monoclonal antibody of claim 164, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 40. The monoclonal antibody of claim 164, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 41. The monoclonal antibody of claim 164, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 42. The method of any one of claims 139 to 158, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 16, and a sequence ID NO: 17 has a heavy chain complementarity determining region 2 (CDR2) sequence having at least 80% identity and a heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 18. The monoclonal antibody of claim 169, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 47. The monoclonal antibody of claim 169, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 48. The monoclonal antibody of claim 169, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 49. The monoclonal antibody of claim 169, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 50. The monoclonal antibody of claim 169, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 51. The monoclonal antibody of claim 169, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 52. The monoclonal antibody of claim 169, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 53. The monoclonal antibody of claim 169, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 54. The method of any one of claims 139 to 177, wherein the monoclonal antibody or antigen-binding fragment thereof comprises an amino acid as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The light chain variable domain (VL) of an amino acid sequence having at least 80% identity. The method of any one of claims 139 to 178, wherein the monoclonal antibody or antigen-binding fragment thereof comprises an amino acid as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of an amino acid sequence that has at least 80% identity. The method of any one of claims 139 to 179, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises an amino acid as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 A light chain variable domain (VL) having an amino acid sequence having at least 80% identity; and comprising an amino acid as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The heavy chain variable domain (VH) of an amino acid sequence that has at least 80% identity. The method of any one of claims 139 to 180, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 19 ( VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 20. The method of any one of claims 139 to 180, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 21 ( VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 22. The method of any one of claims 139 to 180, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 23 ( VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 24. The method of any one of claims 139 to 183, wherein the monoclonal antibody or antigen-binding fragment thereof specifically binds to an ERFE protein. The method of any one of claims 138 to 184, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from the group consisting of whole immunoglobulin, scFv, Fab, F (ab ') ₂ or disulfide-linked Fv. The method of any one of claims 138 to 185, wherein the monoclonal antibody or antigen-binding fragment thereof is IgG or IgM. The method of any one of claims 138 to 186, wherein the monoclonal antibody or fragment thereof is humanized or chimeric. The method of any one of claims 138 to 187, wherein the administering the monoclonal antibody increases the hepcidin content of the individual. The method of any one of claims 138 to 188, wherein the administration of the monoclonal antibody reduces the iron content of the individual. The method of any one of claims 138 to 189, wherein the iron metabolism disease or disorder is selected from the group consisting of: hemochromatosis, HFE mutation hemochromatosis, ferroportin mutation hemochromatosis, Transferrin receptor 2 mutation hemochromatosis, hemojuvelin mutation hemoglobinosis, hepcidin mutation hemoglobinosis, adolescent hemochromatosis, neonatal hemochromatosis, hepcidin deficiency, Transfusional iron overload, thalassemia, intermediate thalassemia, alpha thalassemia, beta thalassemia, myelodysplastic syndrome, polycythemia vera, sideroblastic anemia, porphyria porphyria), delayed-onset skin porphyria (porphyria cutanea tarda), African iron overload, hyperferritinemia, plasma ceruloplasmin deficiency, and anemia without iron transfer protein. The method of any one of claims 138 to 190, wherein the method reduces at least one symptom of a disease or disorder of iron metabolism. The method of claim 191, wherein the symptoms are selected from the group consisting of chronic fatigue, joint pain, abdominal pain, liver disease (cirrhosis, liver cancer), diabetes, irregular heart rhythm, heart attack or heart failure, skin color changes ( (Bronze, grayish green), menstrual loss, loss of libido, osteoarthritis, osteoporosis, hair loss, liver or splenomegaly, impotence, infertility, hypogonadism, hypothyroidism, hypopituitarism, depression Disease, adrenal function problems, early-onset neurodegenerative diseases, elevated blood sugar, elevated liver enzymes, elevated iron (e.g. serum iron, serum ferritin), excessive iron deposition in the liver, excessive iron deposition in the heart, weakness, pale skin , Shortness of breath, dizziness, craving for eating, tingling or crawling feeling in the legs, swelling or pain in the tongue, cold hands and feet, fast or irregular heartbeat, crisp nails, and headaches. The method of any one of claims 138 to 192, wherein the method further comprises phlebotomy or chelation therapy. The method of any one of claims 138 to 192, wherein the treated individual no longer requires phlebotomy or chelation therapy to reduce iron content. The monoclonal antibody of any one of claims 1 to 137, for use in treating a disease or disorder of iron metabolism. The monoclonal antibody of any one of claims 1 to 137, for use in the preparation of a medicament for treating a disease or disorder of iron metabolism. A composition comprising a monoclonal antibody or an antigen-binding fragment thereof and at least one buffer or excipient, wherein the monoclonal antibody or the antigen-binding fragment thereof is selected from the monoclonal antibody of any one of claims 1 to 137 . A composition comprising a monoclonal antibody or an antigen-binding fragment thereof and at least one buffer or excipient, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises and is as shown in SEQ ID NOs: 1-3, 7-9, and 13 At least one of the amino acid sequences described in -15 has a light chain complementarity determining region (CDR) sequence that is at least 80% identical. A composition comprising a monoclonal antibody or an antigen-binding fragment thereof and at least one buffer or excipient, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises and is as follows with SEQ ID NOs: 4-6, 10-12, and 16 At least one of the amino acid sequences described in -18 has a heavy chain complementarity determining region (CDR) sequence that is at least 80% identical. The composition of claim 198 or 199, wherein the monoclonal antibody comprises a) at least 80 with at least one of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15 % Identity light chain complementarity determining region (CDR) sequences; and b) at least 80% with at least one of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18 Consistent heavy chain complementarity determining region (CDR) sequences. The composition of any one of claims 198 to 200, wherein the monoclonal antibody comprises a) and at least two of the amino acid sequences described in SEQ ID NOs: 1-3, 7-9, and 13-15 Or a light chain complementarity determining region (CDR) sequence having at least 80% identity; and b) at least two of the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, and 16-18 Heavy chain complementarity determining region (CDR) sequences with at least 80% identity. The composition of any one of claims 198 to 201, wherein the monoclonal antibody comprises a) having at least 90% of the amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 Identical light chain complementarity determining region (CDR) sequences; and b) heavy chain complementarities with at least 90% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18 Determinant region (CDR) sequence. The composition of any one of claims 198 to 202, wherein the monoclonal antibody comprises a) having at least 95% of the amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 Identical light chain complementarity determining region (CDR) sequences; and b) heavy chain complementarities with at least 95% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18 Determinant region (CDR) sequence. The composition of any one of claims 198 to 203, wherein the monoclonal antibody comprises a) having at least 99% of the amino acid sequence as described in SEQ ID NO: 1-3, 7-9, or 13-15 Identical light chain complementarity determining region (CDR) sequences; and b) heavy chain complementarities with at least 99% identity to the amino acid sequences described in SEQ ID NOs: 4-6, 10-12, or 16-18 Determinant region (CDR) sequence. The composition of any one of claims 198 to 204, wherein the monoclonal antibody comprises a) 100% identical to the amino acid sequence described in SEQ ID NO: 1-3, 7-9, or 13-15 Sex light chain complementarity determining region (CDR) sequences; and b) a heavy chain complementarity determining region having 100% identity to the amino acid sequence described in SEQ ID NO: 4-6, 10-12, or 16-18 (CDR) sequence. The composition of any one of claims 198 to 205, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least 80% of one of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 13 Light chain complementarity determining region 1 (CDR1) sequence of% identity, light chain complementarity determining region 2 having at least 80% identity to one of SEQ ID NO: 2, SEQ ID NO: 8 or SEQ ID NO: 14 (CDR2) sequence, a light chain complementarity determining region 3 (CDR3) sequence having at least 80% identity to one of SEQ ID NO: 3, SEQ ID NO: 9 or SEQ ID NO: 15, and SEQ ID NO: 4.A heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with one of SEQ ID NO: 10 or SEQ ID NO: 16, which is identical to SEQ ID NO: 5, SEQ ID NO: 11 or SEQ ID One of NO: 17 has at least 80% identity to a heavy chain complementarity determining region 2 (CDR2) sequence and at least 80% of one of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 13 % Consensus heavy chain complementarity determining region 3 (CDR3) sequence. The composition of any one of claims 198 to 206, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 1, and SEQ ID NO: 2 has a light chain complementarity determining region 2 (CDR2) sequence with at least 80% identity and a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity. The monoclonal antibody of claim 207, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 31. The monoclonal antibody of claim 207, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 32. The monoclonal antibody of claim 207, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 33. The monoclonal antibody of claim 207, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 34. The composition of any one of claims 198 to 206, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 7, and SEQ ID NO: 8 has a light chain complementarity determining region 2 (CDR2) sequence with at least 80% identity and a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 9. The composition of any one of claims 198 to 206, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 13, and SEQ ID NO: 14 has a light chain complementarity determining region 2 (CDR2) sequence with at least 80% identity and SEQ ID NO: 15 has a light chain complementarity determining region 3 (CDR3) sequence with at least 80% identity. The monoclonal antibody of claim 213, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 43. The monoclonal antibody of claim 213, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 44. The monoclonal antibody of claim 213, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 45. The monoclonal antibody of claim 213, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a light chain complementarity determining region 1 (CDR1) sequence as described in SEQ ID NO: 46. The composition of any one of claims 198 to 217, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 4, and SEQ ID NO: 5 has a heavy chain complementarity determining region 2 (CDR2) sequence with at least 80% identity and a heavy chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 6. The monoclonal antibody of claim 218, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 35. The monoclonal antibody of claim 218, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 36. The monoclonal antibody of claim 218, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 37. The monoclonal antibody of claim 218, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 38. The composition of any one of claims 198 to 217, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 10, and SEQ ID NO: 11 has a heavy chain complementarity determining region 2 (CDR2) sequence with at least 80% identity and a heavy chain complementarity determining region 3 (CDR3) sequence with at least 80% identity with SEQ ID NO: 12. The monoclonal antibody of claim 223, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 39. The monoclonal antibody of claim 223, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 40. The monoclonal antibody of claim 223, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 41. The monoclonal antibody of claim 223, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 42. The composition of any one of claims 198 to 217, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region 1 (CDR1) sequence having at least 80% identity with SEQ ID NO: 16, and SEQ ID NO: 17 has a heavy chain complementarity determining region 2 (CDR2) sequence having at least 80% identity and a heavy chain complementarity determining region 3 (CDR3) sequence having at least 80% identity with SEQ ID NO: 18. The monoclonal antibody of claim 228, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 47. The monoclonal antibody of claim 228, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 48. The monoclonal antibody of claim 228, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 49. The monoclonal antibody of claim 228, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 50. The monoclonal antibody of claim 228, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 51. The monoclonal antibody of claim 228, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 52. The monoclonal antibody of claim 228, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 53. The monoclonal antibody of claim 228, wherein the monoclonal antibody or antigen-binding fragment thereof comprises at least a heavy chain complementarity determining region 2 (CDR2) sequence as described in SEQ ID NO: 54. The composition of any one of claims 198 to 236, wherein the monoclonal antibody or antigen-binding fragment thereof comprises an amino group comprising the amino group as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 The acid sequence has a light chain variable domain (VL) of an amino acid sequence that is at least 80% identical. The composition of any one of claims 198 to 237, wherein the monoclonal antibody or antigen-binding fragment thereof comprises an amino group comprising the amino group as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The acid sequence has a heavy chain variable domain (VH) of an amino acid sequence that is at least 80% identical. The composition of any one of claims 198 to 238, wherein the monoclonal antibody or antigen-binding fragment thereof comprises an amino group comprising the amino group as described in SEQ ID NO: 19, SEQ ID NO: 21, or SEQ ID NO: 23 A light chain variable domain (VL) having an amino acid sequence having at least 80% identity in the acid sequence; and comprising an amino group as described in SEQ ID NO: 20, SEQ ID NO: 22, or SEQ ID NO: 24 The acid sequence has a heavy chain variable domain (VH) of an amino acid sequence that is at least 80% identical. The composition of any one of claims 198 to 239, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 19 (VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 20. The composition of any one of claims 198 to 239, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 21 (VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 22. The composition of any one of claims 198 to 239, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 23 (VL) and a heavy chain variable domain (VH) comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 24. The composition of any one of claims 197 to 242, wherein the monoclonal antibody or antigen-binding fragment thereof specifically binds to an ERFE protein. The composition of any one of claims 197 to 243, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from the group consisting of whole immunoglobulin, scFv, Fab, F (ab ') ₂ or disulfide-linked Fv. The composition of any one of claims 197 to 244, wherein the monoclonal antibody or antigen-binding fragment thereof is IgG or IgM. The composition of any one of claims 197 to 245, wherein the monoclonal antibody or fragment thereof is humanized or chimeric.