Anti-stem cell factor antibodies and methods of blocking the interaction between SCF and c-Kit
The disclosure relates to antibodies and antigen-binding fragments thereof that bind to Stem Cell Factor (SCF). The antibodies and antigen-binding fragments thereof specifically bind to SCF248. The disclosure further relates to methods for making the antibodies, and to methods of use of the antibodies including methods of treatment for inflammatory and/or fibrotic diseases and disorders.
1. An antibody that specifically binds to stem cell factor (SCF), wherein the antibody comprises a heavy chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 1, 2, and 3, respectively; and a light chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 4, 5, and 6, respectively.
2. The antibody of claim 1 , wherein the antibody 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.
3. The antibody of claim 1 , wherein the antibody comprises:
(a) 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;
(b) 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;
(c) 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;
(d) 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; or
(e) 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.
4. The antibody or fragment thereof of claim 1 , comprising:
(i) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 8; and
(ii) a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 16.
5. The antibody of claim 1 , wherein the antibody is humanized.
6. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
7. The antibody of claim 6 , wherein the antibody comprises a human IgG4 domain.
8. The antibody of claim 7 , 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.
9. The antibody of claim 7 , wherein the human IgG4 domain comprises the amino acid sequence of SEQ ID NO: 40.
10. The antibody of claim 6 , wherein the antibody comprises a heavy chain according to SEQ ID NO: 42 and a light chain according to SEQ ID NO: 49; or wherein the antibody comprises a heavy chain according to SEQ ID NO: 43 and a light chain according to SEQ ID NO: 49.
11. The antibody of claim 1 , wherein
(a) the antibody blocks the interaction between SCF and c-Kit;
(b) the antibody causes internalization of SCF; and/or
(c) the antibody specifically binds to SCF248 and does not bind to SCF220.
12. The antibody of claim 1 , wherein the antibody binds to an epitope comprising at least 8 contiguous amino acids of SEQ ID NO: 33, wherein the antibody inhibits the interaction of SCF248 with c-Kit.
13. The antibody or fragment thcrcof of claim 12 , wherein the epitope consists of SEQ ID NO: 33.
14. The antibody or fragment thereof of claim 1 , comprising: a light chain human Ig kappa constant domain.
15. The antibody of claim 14 , wherein the light chain human Ig kappa constant domain comprises the amino acid sequence of SEQ ID NO: 41 .
16. The antibody of claim 1 , comprising: a light chain human Ig lambda constant domain.
17. An anti-stem cell factor (SCF) antibody that specifically binds to SCF, comprising:
(i) a heavy chain, wherein each heavy chain comprises the amino acid sequence of SEQ ID NO: 42; and
(ii) a light chain, wherein each light chain comprises the amino acid sequence of SEQ ID NO: 49.