Combination of an anti-ED—B fibronectin domain antibody—IL-2 fusion protein and gemcitabine
View Patent ↗The invention refers to the use of L19IL2 for treatment of pancreatic cancer. In another embodiment, the invention relates to a combination (i) of a fusion protein, comprising an Interleukin 2 part and an antibody part, specifically recognizing the extra domain B of fibronectin (ED-B-fibronectin), and (ii) gemcitabine.
1. A combination comprising at least (i) a fusion protein and (ii) gemcitabine, wherein the fusion protein comprises
an antibody part comprising a V heavy chain comprising the sequence set forth in SEQ ID NO: 1 and a V light chain comprising the sequence set forth in SEQ ID NO: 2 and which binds to the ED b -fibronectin domain and
an Interleukin-2 part.
2. A combination according to claim 1 ,
wherein the fusion protein has an N-terminal antibody part and a C-terminal Interleukin-2 part or
wherein the fusion protein has an N-terminal Interleukin-2 part and a C-terminal antibody-part.
3. A combination according to claim 1 , wherein the fusion protein has a fusion protein linker connecting the antibody part and the Interleukin-2 part.
4. A combination according to claim 1 , wherein the antibody part specifically binds to the ED b oncofetal fibronectin domain with sub-nanomolar affinity.
5. A combination according to claim 1 , wherein the antibody part comprises one V heavy chain according to SEQ ID NO: 1 and one V light chain according to SEQ ID NO: 2.
6. A combination according to claim 1 , wherein the heavy and the light chain are connected by an antibody linker.
7. A combination according to claim 6 , wherein the antibody linker comprises a sequence comprising at least 90% identity to the sequence set forth in SEQ ID NO: 3.
8. A combination according to claim 1 , wherein the Interleukin-2 part is human Interleukin-2 or a functional variant thereof.
9. A combination according to claim 1 , wherein the Interleukin-2 part comprises a sequence according to SEQ ID NO: 4.
10. A combination according to claim 1 , wherein a fusion protein linker connects the antibody-part and the Interleukin-2 part.
11. A combination according to claim 10 , wherein the fusion protein linker has a length of 1 to 30 amino acids.
12. A combination according to claim 10 , wherein the fusion protein linker comprises a sequence according to SEQ ID NO: 5.
13. A combination according to claim 1 , wherein gemcitabine is gemcitabine hydrochloride.
14. A medicament which comprises the combination according to claim 1 and a solvent.
15. A pharmaceutical composition comprising the combination according to claim 1 and a pharmaceutically acceptable carrier or diluent.
16. A kit comprising, in separate packages, the fusion protein and the gemcitabine according to claim 1 .
17. A method for treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the combination according to claim 1 .
18. A method according to claim 17 , wherein the cancer is non-small cell lung cancer, head and neck cancer, ovarian cancer or breast cancer.
19. A method according to claim 17 , wherein the cancer is pancreatic cancer.
20. A combination according to claim 6 , wherein the antibody linker comprises the sequence set forth in SEQ ID NO: 3.