Compositions comprising antibody-duocarmycin drug conjugates

1. A lyophilized composition comprising an antibody-drug conjugate of formula (I),

a buffering agent, a lyoprotectant, and a surfactant wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-3,200 to 1, wherein mAb is a monoclonal antibody.

2. The composition according to claim 1 wherein the lyoprotectant is a non-reducing saccharide.

3. The composition according to claim 2 , wherein the lyoprotectant is sucrose, trehalose or a mixture thereof.

4. The composition according to claim 1 , wherein the buffering agent is histidine, citrate or succinate.

5. The composition according to claim 1 , wherein the surfactant is an alkyl glycoside, poloxamer or polysorbate.

6. The composition according to claim 1 , wherein the monoclonal antibody is an anti-HER2 antibody.

7. The composition according to claim 1 , consisting essentially of an antibody-drug conjugate of formula (I), a buffering agent, a lyoprotectant, and a surfactant wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-3,200 to 1.

8. The composition according to claim 1 , wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-2,000 to 1.

9. The composition according to claim 8 , wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-1,800 to 1.

10. A process for the preparation of the composition according to claim 1 , comprising the steps of a) freezing a pre-lyophilization aqueous solution of a composition of claim 1 , b) primary drying at a product temperature below the collapse temperature of the composition at a pressure below atmospheric pressure, and c) secondary drying at a product temperature above 0° C. and below the glass transition temperature of the composition at a pressure below atmospheric pressure.

11. The process of claim 10 wherein the freezing step a) comprises an annealing step, wherein the annealing step is performed for 0.5 to 6 hours at a shelf temperature in the range of −25° C. to −10° C.

12. A composition comprising an antibody-drug conjugate of formula (I),

a buffering agent, a lyoprotectant, a surfactant, and water, wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-3,200 to 1, wherein mAb is a monoclonal antibody.

13. The composition according to claim 12 wherein the lyoprotectant is a non-reducing saccharide.

14. The composition according to claim 13 , wherein the lyoprotectant is sucrose, trehalose or a mixture thereof.

15. The composition according to claim 12 , wherein the buffering agent is histidine, citrate or succinate.

16. The composition according to claim 12 , wherein the surfactant is an alkyl glycoside, poloxamer or polysorbate.

17. The composition according to claim 12 , wherein the monoclonal antibody is an anti-HER2 antibody.

18. The composition according to claim 12 , consisting essentially of an antibody-drug conjugate of formula (I), a buffering agent, a lyoprotectant, and a surfactant wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-3,200 to 1.

19. The composition according to claim 12 , wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-2,000 to 1.

20. The composition according to claim 19 , wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-1,800 to 1.

21. The composition according to claim 12 , wherein the antibody-drug conjugate is present in a concentration of 1-30 mg/ml.

22. The composition according to claim 12 , wherein the buffering agent is present in a concentration of 2.5-25 mM.

23. The composition according to claim 12 , wherein the composition has a pH of 5.3-6.0.

24. The composition according to claim 12 , comprising an antibody-drug conjugate of formula (II),

histidine, trehalose, and polysorbate 20, wherein the molar ratio of trehalose to antibody-drug conjugate is about 1,605 to 1, and wherein the antibody-drug conjugate is present in an amount of about 10 mg/ml, the concentration of histidine is about 5 mM, the amount of polysorbate 20 is about 0.01% (mass/volume), and the pH is about 5.7.

25. The composition according to claim 24 consisting essentially of an antibody-drug conjugate of formula (II), histidine, trehalose, and polysorbate 20, wherein the molar ratio of trehalose to antibody-drug conjugate is about 1,605 to 1, and the antibody-drug conjugate is present in an amount of about 10 mg/ml, the concentration of histidine is about 5 mM, the amount of polysorbate 20 is about 0.01% (mass/volume), and the pH is about 5.7.