Humanized antibodies against c-Kit
The invention provides antibodies specifically binding to c-Kit and methods of using such antibodies in stem cell replacement and treatment of cancer.
1. An antibody specifically binding to human c-Kit comprising a mature heavy variable region comprising CDRs H1, H2 and H3 as defined by Kabat of SEQ ID NOS:14-16 respectively, and a mature light chain variable region comprising CDRs L1, L2 and L3 as defined by Kabat of SEQ ID NOS:36-38 respectively.
2. The antibody of claim 1 , wherein the mature heavy chain variable region shows at least 95% sequence identity to SEQ ID NO: 13 , and the mature light chain variable region shows at least 95 % sequence identity to SEQ ID NO: 53 , wherein any variation from SEQ ID NOS: 13 and 53 is outside the CDRs as defined by Kabat.
3. The antibody of claim 2 , wherein heavy chain position 1 by Kabat numbering is E.
4. The antibody of claim 2 , wherein the following positions of the mature light chain variable region according to Kabat numbering are occupied by amino acids as follows:
Position 9 occupied by L;
Position 12 occupied by P;
Position 14 occupied by T;
Position 15 occupied by P;
Position 18 occupied by P;
Position 20 occupied by S;
Position 22 occupied by S;
Position 37 occupied by L;
Position 43 occupied by S;
Position 45 occupied by Q;
Position 74 occupied by K;
Position 77 occupied by R;
Position 78 occupied by V;
Position 79 occupied by E; and
Position 84 occupied by G.
5. The antibody of claim 1 , wherein the mature heavy chain variable region has the amino acid sequence of SEQ ID NO:13 except that position 1 can be E, and the mature light chain variable region has the amino acid sequence of SEQ ID NO:53.
6. The antibody of claim 1 , wherein the mature heavy chain variable region is linked to a heavy chain constant region and the mature light chain variable region is linked to a mature light chain constant region.
7. The antibody of claim 6 , wherein the heavy chain constant region is human IgG1.
8. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
9. The antibody of claim 1 , wherein the mature heavy chain variable region shows at least 98% sequence identity to SEQ ID NO:13 and the mature light chain variable region shows at least 98% sequence identity to SEQ ID NO:53, wherein any variation from SEQ ID NOS:13 and 53 is outside the CDRs as defined by Kabat.
10. The antibody of claim 1 , wherein the mature heavy chain variable region shows at least 99% sequence identity to SEQ ID NO:13 and the mature light chain variable region shows at least 99% sequence identity to SEQ ID NO:53, wherein any variation from SEQ ID NOS:13 and 53 is outside the CDRs as defined by Kabat.
11. The antibody of claim 5 , wherein the mature heavy chain variable region is linked to a heavy chain constant region and the mature light chain variable region is linked to a mature light chain constant region.
12. The antibody of claim 11 , wherein the heavy chain constant region is human IgG1.
13. A pharmaceutical composition comprising the antibody of claim 5 and a pharmaceutically acceptable carrier.
14. An antibody specifically binding to human c-Kit comprising a mature heavy chain variable region having the amino acid sequence of SEQ ID NO:13 and a mature light chain variable region having the amino acid sequence of SEQ ID NO:53, wherein the mature heavy chain variable region is linked to a heavy chain constant region of human IgG1 isotype and the mature light chain variable region is linked to a mature light chain constant region.
15. The antibody of claim 14 expressed from a CHO cell.
16. A pharmaceutical composition comprising the antibody of claim 14 and a pharmaceutically acceptable carrier.