Methods for preparing antibody drug conjugates

Patent metadata

Field	Value
Publication number	US-12090211-B2
Application number	US-202217990988-A
Country	US
Kind code	B2
Filing date	Nov 21, 2022
Priority date	Oct 5, 2016
Publication date	Sep 17, 2024
Grant date	Sep 17, 2024

Abstract

The subject matter described herein is directed to methods of preparing certain antibody-drug conjugates (ADCs) wherein the antibody is linked to the drug through a linker, wherein the drug contains a heteroaryl group having a secondary nitrogen, and the linker is attached to the drug via the secondary nitrogen. The resulting conjugates are useful in treating various diseases and conditions.

First claim

That which is claimed:

1. An antibody-drug conjugate of Formula IV:

or a pharmaceutically acceptable salt thereof, wherein
Ab is an antibody;
R 1 , R 2 , R 3 , and R 4 are independently selected from the group consisting of H, optionally substituted branched or linear C 1 -C 5 alkyl, and optionally substituted C 3 -C 6 cycloalkyl, or R 3 and R 4 taken together with the carbon atom to which they are bound form a C 3 -C 6 cycloalkyl ring,
wherein said optionally substituted alkyl or cycloalkyl may be substituted with alkyl, cycloalkyl, aryl, heteroaryl, hydroxyl, nitrile, halo, alkoxy, haloalkoxy, arylalkoxy, acyloxy, alkylthio, sulfonate, amino, alkylamino, acylamino, carbamoyl, alkylcarbamoyl, or nitro;
D is:

wherein the carbonyl in Formula IV is covalently bonded to the secondary nitrogen in D; and
p is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

2. The antibody-drug conjugate of claim 1 , wherein R 1 , R 2 , R 3 , and R 4 are independently selected from the group consisting of H and optionally substituted branched or linear C 1 -C 5 alkyl.

3. The antibody-drug conjugate of claim 2 , wherein one of R 1 , R 2 , R 3 , and R 4 is optionally substituted branched or linear C 1 -C 5 alkyl and the others are H.

4. The antibody-drug conjugate of claim 3 , wherein said optionally substituted branched or linear C 1 -C 5 alkyl is methyl.

5. The antibody-drug conjugate of claim 4 , wherein R 1 is methyl, and R 2 , R 3 , and R 4 are each H.

6. The antibody-drug conjugate of claim 5 , wherein said antibody-drug conjugate of Formula IV has the structure:

wherein p is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

7. The antibody-drug conjugate of claim 5 , wherein said antibody-drug conjugate of Formula IV has the structure:

wherein p is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

8. The antibody-drug conjugate of claim 1 , wherein said Ab is a cysteine engineered antibody.

9. The antibody-drug conjugate of claim 1 , wherein the antibody binds to HER2 or B7-H4.

10. The antibody-drug conjugate of claim 9 , wherein the antibody binds to HER2.

11. The antibody-drug conjugate of claim 1 , selected from the group consisting of:

wherein p is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

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

wherein the antibody is Anti-HER2 and p is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

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

wherein the antibody is Anti-B7H4 and p is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

Assignees

• Genentech Inc

Inventors

• Pillow Thomas
• DRAGOVICH Peter

Classifications

• A61K47/65

  Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers · CPC title

• C07K16/22

  against growth factors {; against growth regulators} · CPC title

• C07K16/2863

  against receptors for growth factors, growth regulators · CPC title

• A61K47/6803 Primary

  Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates · CPC title

• A61P5/32

  Antioestrogens · CPC title