COMPOSITION AND METHOD FOR THE DIAGNOSIS AND TREATMENT OF IRON-RELATED DISORDERS

1 .- 138 . (canceled)

139 . An anti-Repulsive Guidance Molecule c (RGMc) antibody comprising:

(a) a variable heavy chain region (VH) that comprises a complementary determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO: 11, a CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 13, and a variable light chain region (VL) that comprises complementary determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO: 14, a CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 16;

(b) a VH that comprises a complementary determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO: 23, a CDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 25, and a VL that comprises complementary determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO: 26, a CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 28; or

(c) a VH that comprises a complementary determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO: 29, a CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 31, and a VL that comprises complementary determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO: 32, a CDR2 comprising the amino acid sequence of SEQ ID NO: 33, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 34.

140 . The antibody of claim 139 , wherein the antibody comprises:

(a) a VH comprising the amino acid sequence of SEQ ID NO: 3, and a VL comprising the amino acid sequence of SEQ ID NO: 4;

(b) a VH comprising the amino acid sequence of SEQ ID NO: 7, and a VL comprising the amino acid sequence of SEQ ID NO: 8; or

(c) a VH comprising the amino acid sequence of SEQ ID NO: 9, and a VL comprising the amino acid sequence of SEQ ID NO: 10.

141 . The antibody of claim 139 , wherein the antibody comprises a heavy chain constant domain.

142 . The antibody of claim 141 , wherein the heavy chain constant domain is a human IgG1 constant domain.

143 . The antibody of claim 139 , wherein the antibody comprises a light chain constant domain.

144 . The antibody of claim 139 , wherein the antibody is affinity matured.

145 . A nucleic acid encoding the VH and/or VL of the antibody of claim 139 .

146 . A nucleic acid encoding the heavy chain and/or light chain of the antibody of claim 139 .

147 . A host cell comprising the nucleic acid of claim 145 .

148 . A host cell comprising the nucleic acid of claim 146 .

149 . A method of producing the antibody of claim 139 , the method comprising culturing the host cell of claim 147 under condition suitable for expressing the antibody.

150 . A method comprising administering the antibody of claim 139 to a subject having anemia of chronic diseases (ACD) or anemia of chronic kidney disease.

151 . The method of claim 150 , wherein the administration results in inhibition of RGMc activity in the subject and wherein the inhibition of RGMc activity affects iron metabolism in the subject.

152 . The method of claim 151 , wherein the inhibition of RGMc activity results in decreased hepcidin expression in the subject.

153 . The method of claim 150 , wherein the subject has a serum hepcidin level higher than that of a normal control.

154 . The method of claim 150 , wherein the subject has a serum hepcidin level higher than 300 mg/l prior to administration of the antibody.

155 . The method of claim 150 , wherein the subject has a hemoglobin level of lower than 15.5 g/dl prior to administration of the antibody.

156 . The method of claim 150 , wherein the subject has a transferrin saturation of less than 25% prior to administration of the antibody.

157 . The method of claim 139 , wherein the subject has a total iron binding capacity of lower than 50% prior to administration of the antibody.

158 . The method of claim 150 , wherein the subject has a serum iron level of less than 60 μg/dl prior to administration of the antibody.