Composition and method for the diagnosis and treatment of iron-related disorders
Provided herein are methods of using the antibodies that bind to RGMc to treat and diagnose iron-related disorders.
1. A humanized monoclonal anti-Repulsive Guidance Molecule c (RGMc) antibody that comprises a variable heavy chain region comprising a complementary determining region (CDR)1 with an amino acid sequence set forth in SEQ ID NO:17, a CDR2 with an amino acid sequence set forth in SEQ ID NO:18; a CDR3 with an amino acid sequence set forth in SEQ ID NO:19; and a variable light chain region comprising a CDR1 with an amino acid sequence set forth in SEQ ID NO:20, a CDR2 with an amino acid sequence set forth in SEQ ID NO:21, and a CDR3 with an amino acid sequence set forth in SEQ ID NO:22.
2. The humanized monoclonal anti-RGMc antibody of claim 1 , wherein the antibody is affinity matured.
3. The humanized monoclonal anti-RGMc antibody of claim 2 , wherein the variable light chain region has the amino acid sequence set forth in SEQ ID NO:6.
4. The humanized monoclonal anti-RGMc antibody of claim 3 , wherein the antibody comprises a heavy chain immunoglobulin constant domain, which is a human IgG1 constant domain.
5. The humanized monoclonal anti-RGMc antibody of claim 1 , wherein the variable heavy chain region has the amino acid sequence set forth in SEQ ID NO:5 with up to one amino acid difference in a framework region.
6. The humanized monoclonal anti-RGMc antibody of claim 3 , wherein the variable heavy chain region has the amino acid sequence set forth in SEQ ID NO:5 with up to one amino acid difference in a framework region.
7. The humanized monoclonal anti-RGMc antibody of claim 5 , wherein the antibody comprises a heavy chain immunoglobulin constant domain, which is a human IgG1 constant domain.
8. The humanized monoclonal anti-RGMc antibody of claim 6 , wherein the antibody comprises a heavy chain immunoglobulin constant domain, which is a human IgG1 constant domain.
9. A pharmaceutical composition comprising the humanized monoclonal antibody of claim 1 and a pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising the humanized monoclonal antibody of claim 8 and a pharmaceutically acceptable carrier.
11. The pharmaceutical composition of claim 9 , wherein the humanized monoclonal antibody and pharmaceutically acceptable carrier are in a lyophilized form.
12. The pharmaceutical composition of claim 10 , wherein the humanized monoclonal antibody and pharmaceutically acceptable carrier are in a lyophilized form.
13. The pharmaceutical composition of claim 9 , wherein the humanized monoclonal antibody and pharmaceutically acceptable carrier are in a solution form.
14. The pharmaceutical composition of claim 10 , wherein the humanized monoclonal antibody and pharmaceutically acceptable carrier are in a solution form.