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1. WO2020112687 - ANTICORPS HUMANISÉS DIRIGÉS CONTRE C-KIT

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

What is claimed is:

1. An antibody specifically binding to human c-Kit comprising a mature heavy variable region comprising CDRs HI, H2 and H3 as defined by Kabat of SEQ ID NOS:2-4 respectively, and a mature light chain variable region comprising CDRs LI, L2 and L3 as defined by Kabat of SEQ ID NOS:6-8 respectively except that 1, 2, or 3 CDR residue substitutions is/are present selected from N to A at heavy chain position 60, K to Q at heavy chain position 64 and N to Q at light chain position 30, positions being numbered according to Kabat.

2. The antibody of claim 1, wherein CDRs HI, H2 and H3 as defined by Kabat are SEQ ID NOS:2-4 respectively, and CDRs LI, L2 and L3 as defined by Kabat are SEQ ID NOS:6-8 respectively except that the substitutions of K to Q at heavy chain position 64 and N to Q at light chain position 30 are present.

3. The antibody of claim 1, wherein CDRs HI, H2 and H3 as defined by Kabat are SEQ ID NOS:2-4 respectively, and CDRs LI, L2 and L3 as defined by Kabat are SEQ ID NOS:6-8 respectively except that the substitutions of N to A at heavy chain position 60, K to Q at heavy chain position 64 and N to Q at light chain position 30 are present.

4. The antibody of any preceding claim, wherein the mature heavy chain variable region shows at least 85, 90, 95, 98, 99%% sequence identity to SEQ ID NO:13, 17 or 21 (AH2, AH3 or AH4) and the mature light chain variable region shows at least 85, 90, 95, 98, 99 % sequence identity to SEQ ID NO: SEQ ID NO:53 (NL2), wherein any variation from the indicated SEQ ID NOS. is outside the CDRs as defined by Kabat.

5. The antibody of claim 4, wherein heavy chain position 1 by Kabat numbering is E.

6. The antibody of any preceding claim, wherein the following positions of the mature light chain variable region 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

Position 84 occupied by G.

7. The antibody of claim 1, wherein the mature heavy chain variable region has a sequence selected from SEQ ID NO:13, 17 or 21 except that position 1 can be E, and the mature light chain variable region has a sequence of SEQ ID NO:53.

8. The antibody of any preceding claim, 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.

9. The antibody of claim 7, wherein the heavy chain constant region is human IgGl.

10. The antibody of any preceding claim having enhanced binding to human c-Kit relative to

AMG191.

11. The antibody of any preceding claim having enhanced ADCP relative to AMG191-lgGl.

12. The antibody of any preceding claim having enhanced ADCC relative to AMG191-lgGl.

13. A pharmaceutical composition comprising an antibody of any preceding claim and a pharmaceutically acceptable carrier.

14. A method of ablating endogenous HSPCs comprising administering an effective regime of antibody of any preceding claim to a subject in need of ablation.

15. A method of treating a cancer expressing c-Kit comprising administering an effective regime of an antibody of any preceding claim to a subject having the cancer.