Antibody drug conjugates (ADCS) having enzymatically cleavable groups

Patent metadata

Field	Value
Publication number	US-11478554-B2
Application number	US-202117464565-A
Country	US
Kind code	B2
Filing date	Sep 1, 2021
Priority date	Dec 21, 2016
Publication date	Oct 25, 2022
Grant date	Oct 25, 2022

Abstract

The invention relates to novel binder-drug conjugates (ADCs) having improved properties, to active metabolites of these ADCs and to processes for their preparation. The present invention furthermore relates to the use of these conjugates for the treatment and/or prevention of diseases and to the use of these conjugates for preparing medicaments for treatment and/or prevention of diseases, in particular hyperproliferative and/or angiogenic disorders such as, for example, cancer diseases.

First claim

The invention claimed is:

1. An antibody or antigen-binding antibody fragment that binds to CXCR5, comprising a variable heavy chain comprising the variable CDR1 sequence of the heavy chain as shown in SEQ ID NO: 92, the variable CDR2 sequence of the heavy chain as shown in SEQ ID NO: 93, and the variable CDR3 sequence of the heavy chain as shown in SEQ ID NO: 94; and a variable light chain comprising the variable CDR1 sequence of the light chain as shown in SEQ ID NO: 96, the variable CDR2 sequence of the light chain as shown in SEQ ID NO: 97, and the variable CDR3 sequence of the light chain as shown in SEQ ID NO: 98.

2. The antibody or antigen-binding antibody fragment of claim 1 , wherein the variable heavy chain comprises a sequence at least 98% identical to SEQ ID NO: 91.

3. The antibody or antigen-binding antibody fragment of claim 1 , wherein the variable heavy chain comprises SEQ ID NO: 91.

4. The antibody or antigen-binding antibody fragment of claim 1 , wherein the variable light chain comprises a sequence at least 98% identical to SEQ ID NO: 95.

5. The antibody or antigen-binding antibody fragment of claim 2 , wherein the variable light chain comprises a sequence at least 98% identical to SEQ ID NO: 95.

6. The antibody or antigen-binding antibody fragment of claim 3 , wherein the variable light chain comprises a sequence at least 98% identical to SEQ ID NO: 95.

7. The antibody or antigen-binding antibody fragment of claim 1 , wherein the variable light chain comprises SEQ ID NO: 95.

8. The antibody or antigen-binding antibody fragment of claim 2 , wherein the variable light chain comprises SEQ ID NO: 95.

9. The antibody or antigen-binding antibody fragment of claim 3 , wherein the variable light chain comprises SEQ ID NO: 95.

10. The antibody or antigen-binding antibody fragment of claim 1 , comprising a heavy chain comprising SEQ ID NO: 101.

11. The antibody or antigen-binding antibody fragment of claim 1 , comprising a light chain comprising SEQ ID NO: 105.

12. The antibody or antigen-binding antibody fragment of claim 10 , comprising a light chain comprising SEQ ID NO: 105.

13. A method for treatment of a disease associated with CXCR5 expression, comprising administering to a patient in need thereof an effective amount of the antibody or antigen-binding antibody fragment of claim 1 .

14. A method for treatment of a disease associated with CXCR5 expression, comprising administering to a patient in need thereof an effective amount of the antibody or antigen-binding antibody fragment of claim 9 .

15. A conjugate comprising the antibody or antigen-binding antibody fragment of claim 1 , and a chemotherapeutic.

16. The conjugate of claim 15 , wherein the chemotherapeutic comprises an inhibitor of kinesin spindle protein.

17. A method for treatment of a disease associated with CXCR5 expression, comprising administering to a patient in need thereof an effective amount of the conjugate of claim 16 .

18. A conjugate comprising the antibody or antigen-binding antibody fragment of claim 9 , and a chemotherapeutic.

19. The conjugate of claim 18 , wherein the chemotherapeutic comprises an inhibitor of kinesin spindle protein.

20. A method for treatment of a disease associated with CXCR5 expression, comprising administering to a patient in need thereof an effective amount of the conjugate of claim 19 .

Assignees

• Bayer Pharma AG
• Bayer Ag

Inventors

• Lerchen Hans-Georg
• Rebstock Anne-Sophie
• Stelte-Ludwig Beatrix
• Kirchhoff Dennis
• Dietz Lisa
• Mahlert Christoph
• Greven Simone
• Märsch Stephan
• Berndt Sandra
• Sommer Anette
• Hammer Stefanie

Classifications

• A61K47/6889 Primary

  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 title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/68 Primary

  the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07K16/2827

  against B7 molecules, e.g. CD80, CD86 · CPC title