ANTI-STEM CELL FACTOR ANTIBODIES AND METHODS OF USE THEREOF IN RENAL DISEASE
The disclosure relates to methods of use in renal diseases and disorders of antibodies and antigen-binding fragments thereof that bind to Stem Cell Factor (SCF). The antibodies and antigen-binding fragments thereof specifically bind to SCF248 and are useful for treating inflammatory and fibrotic renal disorders.
1 . A method for treating an inflammatory or fibrotic renal disease in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment thereof that specifically binds to stem cell factor (SCF), wherein the antibody or antigen binding fragment thereof comprises heavy chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 1, 2, and 3, respectively; and light chain CDR1, CDR2, and CDR3 according to SEQ ID NOs: 4, 5, and 6, respectively.
2 . The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region having at least 80% identity to a sequence selected from SEQ ID NOs: 7, 8, 9, 10, and 11.
3 . The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region having at least 90% identity to a sequence selected from SEQ ID NOs: 7, 8, 9, 10, and 11.
4 . The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain variable region having at least 80% identity to a sequence selected from SEQ ID NOs: 13, 14, 15, and 16.
5 . The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain variable region having at least 90% identity to a sequence selected from SEQ ID NOs: 13, 14, 15, and 16.
6 . The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region amino acid sequence selected from SEQ ID NOs: 7, 8, 9, 10, and 11; and a light chain variable region amino acid sequence selected from SEQ ID NOs: 13, 14, 15, and 16.
7 . The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region amino acid sequence according to SEQ ID NO: 7 and a light chain variable region amino acid sequence according to SEQ ID NO: 16.
8 . The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region amino acid sequence according to SEQ ID NO: 8 and a light chain variable region amino acid sequence according to SEQ ID NO: 16.
9 . The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region amino acid sequence according to SEQ ID NO: 9 and a light chain variable region amino acid sequence according to SEQ ID NO: 16.
10 . The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region amino acid sequence according to SEQ ID NO: 10 and a light chain variable region amino acid sequence according to SEQ ID NO: 16.
11 . The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region amino acid sequence according to SEQ ID NO: 11 and a light chain variable region amino acid sequence according to SEQ ID NO: 16.
12 . The method of claim 1 , wherein the antibody or fragment thereof is humanized.
13 . The method of claim 1 , wherein the antibody is a monoclonal antibody.
14 . The method of claim 13 , wherein the antibody comprises a human IgG4 domain.
15 . The method of claim 14 , wherein the IgG4 domain comprises a S241P mutation at amino acid residue 241 and an L248E mutation at amino acid residue 248, wherein the numbering of the residues is that of the Kabat numbering system.
16 . The method of claim 13 , wherein the antibody comprises a heavy chain according to SEQ ID NO: 42 and a light chain according to SEQ ID NO: 49.
17 . The method of claim 13 , wherein the antibody comprises a heavy chain according to SEQ ID NO: 43 and a light chain according to SEQ ID NO: 49.
18 . The method of claim 1 , wherein the antibody or fragment thereof specifically binds to SCF248.
19 . The method of claim 1 , wherein the antibody does not bind to SCF220.
20 . The method of claim 1 , wherein the inflammatory or fibrotic renal disease is selected from the group consisting of chronic kidney disease (CKD), end stage renal disease (ERSD), renal fibrosis, glomerulonephritis, and nephropathy.
21 . The method of claim 20 , wherein the nephropathy or glomerulonephritis is IgA nephropathy, diabetic nephropathy, focal segmental glomerulosclerosis, rapidly progressive glomerulonephritis, crescentic glomerulonephritis, lupus nephritis, hypertensive nephropathy, or diabetic nephropathy.