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 composition comprising an anti-Repulsive Guidance Molecule c (RGMc) antibody that comprises:
(i) a variable heavy chain region comprising a complementary determining region (CDR)1 with the amino acid sequence set forth in SEQ ID NO: 17, a CDR2 with the amino acid sequence set forth in SEQ ID NO: 18, a CDR3 with the amino acid sequence set forth in SEQ ID NO: 19, and a variable light chain region comprising a CDR1 with the amino acid sequence set forth in SEQ ID NO: 20, a CDR2 with the amino acid sequence set forth in SEQ ID NO: 21, and a CDR3 with the amino acid sequence set forth in SEQ ID NO:22; and
(ii) a human IgG1 constant domain.
2. The composition of claim 1 , wherein the antibody is affinity matured.
3. The composition of claim 1 , wherein the variable light chain region has the amino acid sequence set forth in SEQ ID NO: 6.
4. The composition 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.
5. The composition 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.
6. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
7. The composition of claim 1 , wherein the composition is in a lyophilized form.
8. The composition of claim 1 , wherein the composition is in a solution form.
9. The composition of claim 5 , wherein the composition is in a lyophilized form.
10. The composition of claim 5 , wherein the composition is in a solution form.
11. A composition comprising an anti-Repulsive Guidance Molecule c (RGMc) antibody that comprises:
a variable heavy chain region linked to a heavy chain constant domain, the heavy chain variable region comprises a complementary determining region (CDR)1
comprising the amino acid sequence set forth in SEQ ID NO: 17, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 18, a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 19, and
a variable light chain region linked to a light chain constant domain, the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 20, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 21, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:22.
12. The composition of claim 11 , wherein the antibody is affinity matured.
13. The composition of claim 11 , wherein the variable light chain region has the amino acid sequence set forth in SEQ ID NO: 6.
14. The composition of claim 11 , 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.
15. The composition of claim 13 , 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.
16. The composition of claim 11 , further comprising a pharmaceutically acceptable carrier.
17. The composition of claim 11 , wherein the composition is in a lyophilized form.
18. The composition of claim 11 , wherein the composition is in a solution form.
19. The composition of claim 15 , wherein the composition is in a lyophilized form.
20. The composition of claim 15 , wherein the composition is in a solution form.