Methods of inhibition of protein fucosylation in vivo using fucose analogs
View Patent ↗The invention provides methods and compositions for the inhibition of fucosylation of proteins, including antibodies, in vivo by administration of a fucose analog.
1. A method for the treatment of cancer in a human in need thereof, comprising administering orally to the human a therapeutically effective amount of a fucose analog, or a composition thereof,
wherein the cancer is a solid tumor having protein fucosylation; and
wherein each fucose analog has formulae (V) or (VI):
or a biologically acceptable salt or solvate thereof, wherein each fucose analog of formula (V) or (VI) can be the alpha or beta anomer or the corresponding aldose form;
wherein each of R 1 , R 3 , and R 4 is independently selected from the group consisting of —OH and —OC(O)C 1 -C 10 alkyl, R 2 is F, R 2a and R 3a are each H, and R 5 is —CH 3 .
2. The method of claim 1 wherein said fucose analog is 2-deoxy-2-fluoro-L-fucose.
3. The method of claim 1 wherein said fucose analog is 2-deoxy-2-fluoro-L-fucose peracetate.
4. The method of claim 1 further comprising administering a tumor-associated antigen or an antigenic fragment thereof as an immunogen.
5. The method of claim 1 further comprising administering a chemotherapeutic agent.
6. The method of claim 1 wherein the solid tumor is breast cancer.
7. The method of claim 1 wherein the solid tumor is lung cancer.
8. The method of claim 1 wherein the solid tumor is renal cell carcinoma.
9. The method of claim 1 wherein administration of the therapeutically effective amount is in the form of one or more dosage units.