ANTIBODY DRUG CONJUGATES

• US 20190321484A1
• Filed: 11/21/2017
• Published: 10/24/2019
• Est. Priority Date: 11/22/2016
• Status: Active Application

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: VONDENHOFF, Gaston Hubertus Maria, TRENKER, Stefan
• Application Number:
  US16/462,274
• Publication Number:
  US 20190321484A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 47/6803 Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
• CPC Class Codes: A61K 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61K 47/6855 the tumour determinant being from breast cancer cell
• CPC Class Codes: A61K 47/6889 Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention pertains to an antibody-drug conjugate comprising an antibody, ferric iron, and at least one drug molecule, and to a pharmaceutical composition comprising the antibody-drug conjugate. The invention further relates to the use of the antibody-drug conjugates in the treatment of diseases, e.g. cancer.

Claims

1. An antibody-drug conjugate comprising an antibody, at least one ferric iron bound to the antibody, and at least one drug molecule bound to the ferric iron.

2. The antibody-drug conjugate of claim 1, wherein the drug molecule is not released from the antibody-drug conjugate when the antibody-drug conjugate is in blood.

3. The antibody-drug conjugate of claim 1, wherein the drug molecule is released from the antibody-drug conjugate when the antibody-drug conjugate is in the endosomal compartment of a cell.

4. The antibody-drug conjugate of claim 1, wherein at least two drug molecules are bound to one ferric iron.

5. The antibody-drug conjugate of claim 1, wherein the average number of drug molecules per antibody in said conjugate is at least 10.

6. The antibody-drug conjugate of claim 1, wherein the drug molecule is an anti-cancer agent.

7. The antibody-drug conjugate of claim 1, wherein the antibody is capable of binding to an antigen expressed on a tumor cell.

8. The antibody-drug conjugate of claim 1, wherein the drug molecule comprises an iron complexing moiety that binds to the ferric iron.

9. The antibody-drug conjugate of claim 1, wherein the drug molecule is coupled to an iron complexing moiety which binds to the ferric iron.

10. The antibody-drug conjugate of claim 8, or wherein said iron complexing moiety is selected from the group consisting of a hydroxamate moiety, a catecholate moiety and a carboxylate moiety.

11. The antibody-drug conjugate of claim 1, having the structure:

Ab[-L1-Me (-L2-D)_n]_m,

wherein

Ab is the antibody,

L1 is a first linker,

Me is the ferric iron,

L2 is a second linker or absent,

D is the drug molecule,

m ranges from 1 to 10, and

n ranges from 1 to 3.

12. The antibody-drug conjugate of claim 1, wherein the drug molecule is released from the ferric iron if the ferric iron is reduced.

13. The antibody-drug conjugate of claim 1, wherein the drug molecule is released from the ferric iron at a pH of less than 5.

14. The antibody-drug conjugate of claim 1, which is stable at pH 8.

15. The antibody-drug conjugate of claim 1, which is stable at pH 5.

16. A pharmaceutical composition comprising the antibody-drug conjugate of claim 1.

17. A method of treating disease in a patient in need thereof, said method comprising the step of administering to said patient an effective amount of the antibody-drug conjugate of claim 1, or a pharmaceutical composition comprising said antibody-drug conjugate.

18. The method of claim 17, wherein said disease is cancer.

19. A method of preventing or reducing the release of a drug molecule from an antibody-drug conjugate in blood, said method comprising the step of complexing a ferric iron with said antibody and said drug molecule to form said antibody-drug conjugate.

20. The method of claim 19, wherein the drug molecule is released from the antibody-drug conjugate in the endosomal compartment of a cell in said patient.

21. The method of claim 19, wherein the antibody-drug conjugate is comprised of an antibody, at least one ferric iron bound to the antibody, and at least one drug molecule hound to the ferric iron.

22. (canceled)

23. (canceled)

24. (canceled)