Combination therapy involving antibodies against claudin 18.2 for treatment of metastatic pancreatic adenocarcinoma

Patent metadata

Field	Value
Publication number	US-11826402-B2
Application number	US-202017066232-A
Country	US
Kind code	B2
Filing date	Oct 8, 2020
Priority date	Feb 20, 2013
Publication date	Nov 28, 2023
Grant date	Nov 28, 2023

Abstract

The present invention provides a combination therapy for effectively treating and/or preventing diseases associated with cells expressing CLDN18.2, including cancer diseases such as pancreatic cancer and metastases thereof.

First claim

The invention claimed is:

1. A method for treating metastatic pancreatic adenocarcinoma in a patient in need thereof, wherein the metastatic pancreatic adenocarcinoma is characterized by cells expressing claudin 18 splice variant 2 (CLDN18.2), the method comprising:
administering an anti-CLDN18.2 antibody to the patient, wherein the antibody comprises a heavy chain variable region (VH) having an amino acid sequence represented by SEQ ID NO: 32 and a light chain variable region (VL) having an amino acid sequence represented by SEQ ID NO: 39, and wherein the antibody has the ability of binding to CLDN18.2 and mediates killing of cells expressing CLDN18.2,
wherein the method further comprises administering a chemotherapy to the patient, wherein the chemotherapy comprises gemcitabine and/or a taxane, wherein the taxane is albumin-bound paclitaxel.

2. The method of claim 1 , wherein the chemotherapy comprises a combination of gemcitabine and albumin-bound paclitaxel.

3. The method of claim 2 , wherein the combination is administered repeatedly according to a combination dosing regimen, wherein the combination dosing regimen comprises once weekly administration for 3 of 4 weeks.

4. The method of claim 3 , wherein the antibody is administered repeatedly according to antibody dosing regimen, wherein the antibody dosing regimen comprises an initial dose of up to 1000 mg/m 2 followed by repeated doses of 300 to 600 mg/m 2 .

5. The method of claim 4 , wherein the antibody is a chimeric antibody comprising a human kappa light chain constant region and a human IgG1 heavy chain constant region.

6. The method of claim 5 , wherein the human kappa light chain constant region is allotype Km(3) and the human IgG1 heavy chain constant region is allotype G1m(3).

7. The method of claim 4 , wherein the anti-CLDN18.2 antibody comprises a heavy chain having an amino acid sequence represented by SEQ ID NO: 17 and a light chain having an amino acid represented by SEQ ID NO: 24.

Assignees

• Astellas Pharma Inc
• Tron Translationale Onkologie An Der Univ Der Johannes Gutenberg Univ Mainz Gemeinnutzige Gmbh
• Tron Translationale Onkologie An Der Univ

Inventors

• Sahin Ugur
• Tureci Ozlem
• Mitnacht-Kraus Rita
• Woll Stefan
• Jacobs Stefan
• Heinz Cornelia

Classifications

• A61K38/2013 Primary

  IL-2 · CPC title

• A61K31/555 Primary

  containing heavy metals, e.g. hemin, hematin, melarsoprol · CPC title

• A61K31/7068

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title

• A61K39/39558 Primary

  against tumor tissues, cells, antigens · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title