Antibody drug conjugate (ADC) targeting Nectin 4 and comprising an exatecan payload

Patent metadata

Field	Value
Publication number	US-12419964-B2
Application number	US-202418904628-A
Country	US
Kind code	B2
Filing date	Oct 2, 2024
Priority date	Oct 2, 2023
Publication date	Sep 23, 2025
Grant date	Sep 23, 2025

Abstract

The present disclosure provides Nectin-4 antibody drug conjugates (ADCs) comprising exatecan and pharmaceutical compositions thereof, and methods of using the ADCs for the treatment of cancer.

First claim

What is claimed is:

1. An antibody-drug conjugate (ADC) of the formula:

wherein:
Ab is an antibody that binds human Nectin-4 and comprises a heavy chain (HC) and a light chain (LC), wherein:
Ab comprises a HC of SEQ ID NO:5 and a LC of SEQ ID NO:6, DAR is 8, and the Ab is conjugated via cysteines at positions C222, C228, C231 of the HC and via a cysteine of C214 of the LC.

2. The ADC of claim 1 , wherein the Ab has a human IgG1 isotype.

3. A composition comprising the ADC of claim 1 , wherein at least about 95% of the ADC in the composition has a DAR of 8.

4. A pharmaceutical composition comprising the ADC of claim 1 , and one or more pharmaceutically acceptable carriers, diluents, or excipients.

5. A method of treating cancer characterized by expression of Nectin-4, the method comprising administering to a patient in need thereof, an effective amount of the ADC of claim 1 .

6. The method of claim 5 , wherein the cancer is urothelial carcinoma, breast cancer, lung cancer, gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, head and neck cancer, ovarian cancer, or prostate cancer.

7. The method of claim 5 , wherein the cancer is urothelial cancer.

8. The method of claim 5 , wherein the patient previously was administered enfortumab vedotin as a first-line, second-line, or third-line treatment and the effective amount of the ADC is subsequently administered.

9. The method of claim 8 , wherein the cancer has relapsed after enfortumab vedotin was administered as a treatment.

10. The method of claim 8 , wherein the cancer has become refractory to treatment with enfortumab vedotin after enfortumab vedotin was administered as a treatment.

11. The method of claim 5 , wherein the cancer is resistant to treatment with enfortumab vedotin.

Assignees

• Lilly Co Eli
• Univ Aix Marseille
• Inst Nat Sante Rech Med
• Inst Jean Paoli & Irene Calmettes
• Centre National De La Rech Scientifique—Cnrs
• Mablink Bioscience
• Univ Claude Bernard Lyon

Inventors

• Elands Jacobus Petrus Maria
• Fares Joanna
• Fournet Guy
• Joseph Benoit
• Lhospice Florence
• Lopez Marc
• Olive Daniel
• Preville Xavier
• Viricel Warren

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title

• A61K47/6889

  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 title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title