Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation

1. A mammalian cell culture medium for the production of antibodies or antibody derivatives having reduced core fucosylation, comprising a mammalian cell or cell line that expresses an antibody or derivative thereof, and an effective amount of a fucose analog

wherein the fucose analog is selected from the group consisting of one of the following formulae (I) or (II):

or a biologically acceptable salt or solvate thereof, wherein:

each of formula (I) or (II) can be the alpha or beta anomer or the corresponding aldose form;

each of R 1 -R 4 is independently selected from the group consisting of —OH, —OC(O)H, —OC(O)C 1 -C 10 alkyl, —OC(O)C 2 -C 10 alkenyl, —OC(O)C 2 -C 10 alkynyl, —OC(O)aryl, —OC(O)heterocycle, —OC(O)C 1 -C 10 alkylene(aryl), —OC(O)C 2 -C 10 alkenylene(aryl), —OC(O)C 2 -C 10 alkynyl(aryl), —OC(O)C 1 -C 10 alkylene heterocycle, —OC(O)C 2 -C 10 alkenylene(heterocycle), —OC(O)C 2 -C 10 alkynyl heterocycle, —OCH 2 OC(O) alkyl, —OCH 2 OC(O)O alkyl, —OCH 2 OC(O) aryl, —OCH 2 OC(O)O aryl, —OC(O)CH 2 O(CH 2 CH 2 O) n CH 3 , —OC(O)CH 2 CH 2 O(CH 2 CH 2 O) n CH 3 , silyl, and —OC 1 -C 10 alkyl, wherein each n is an integer independently selected from 0-5; and

R 5 is selected from the group consisting of —C≡CH, —C≡CCH 3 , —CH 2 C≡CH, C(O)OCH 3 , —CH(OAc)CH 3 , —CN, —CH 2 CN, —CH 2 X (wherein X is Br, Cl or I), and methoxiran.

2. The culture medium of claim 1 wherein R 5 is selected from the group consisting of —C≡CH, —C≡CH 3 , C(O)OCH 3 , —CH 2 CN, and —CH 2 Br.

3. The culture medium of claim 1 wherein R 5 is —C≡CH and R 1 -R 4 is —OAc.

4. The culture medium of claim 1 , which is free of added animal protein.

5. The culture medium of claim 1 , which is free of serum.

6. The culture medium of claim 1 , which is free of added fucose.

7. The culture medium of claim 1 , which is a powder.

8. The culture medium of claim 1 , which is a liquid.

9. The culture medium of claim 1 , wherein each of R 1 -R 4 is independently selected from the group consisting of —OH and —OC(O)C 1 -C 10 alkyl.

10. The culture medium of claim 1 , wherein each of R 1 -R 4 is independently selected from the group consisting of —OH and —OAc.

11. The culture medium of claim 1 , wherein R 5 is selected from the group consisting of —C≡CH and —C≡CCH 3 .

12. The culture medium of claim 1 , wherein R 5 is —C(O)OCH 3 , —CH 2 CN, or —CH 2 BR.

13. The culture medium of claim 1 wherein the effective amount is an amount of the analog that is sufficient to decrease fucose incorporation into a complex N-glycoside-linked sugar chain of an antibody or antibody derivative by at least 90%.

14. The culture medium of claim 1 , which:

(i) is free of added animal protein;

(ii) is free of serum;

(iii) is free of added fucose; and

(iv) is a powder or a liquid.

15. The culture medium of claim 13 , which:

(i) is free of added animal protein;

(ii) is free of serum;

(iii) is free of added fucose; and

(iv) is a powder or a liquid.

16. The culture medium of claim 14 wherein the effective amount is an amount of the analog that is sufficient to decrease fucose incorporation into a complex N-glycoside-linked sugar chain of an antibody or antibody derivative by at least 90%.

17. The culture medium of claim 2 wherein the antibody or antibody derivative is a humanized or human antibody or antibody derivative.

18. The culture medium of claim 2 wherein the mammalian cell culture medium is a Chinese hamster ovary cell culture medium.

19. The culture medium of claim 14 wherein the antibody or antibody derivative is a humanized or human antibody or antibody derivative.

20. The culture medium of claim 14 wherein the mammalian cell culture medium is a Chinese hamster ovary cell culture medium.