Agents for treatment of claudin expressing cancer diseases

Patent metadata

Field	Value
Publication number	US-10093736-B2
Application number	US-201314442445-A
Country	US
Kind code	B2
Filing date	Nov 12, 2013
Priority date	Nov 13, 2012
Publication date	Oct 9, 2018
Grant date	Oct 9, 2018

Abstract

The present invention provides binding agents that contain a binding domain that is specific for CD3 allowing binding to T cells and a binding domain that is specific for a tumor-associated claudin molecule and methods of using these binding agents or nucleic acids encoding therefor for treating cancer.

First claim

The invention claimed is:

1. A method of treating a cancer disease comprising administering to a patient a binding agent comprising at least two binding domains, wherein a first binding domain binds to claudin (CLDN) and a second binding domain binds to CD3, wherein the binding agent comprises a variable domain of a heavy chain of an immunoglobulin (VH) with a specificity for a claudin antigen (VH(CLDN)), a variable domain of a light chain of an immunoglobulin (VL) with a specificity for a claudin antigen (VL(CLDN)), a variable domain of a heavy chain of an immunoglobulin (VH) with a specificity for CD3 (VH(CD3)), and a variable domain of a light chain of an immunoglobulin (VL) with a specificity for CD3 (VL(CD3)) wherein said CLDN is CLDN18.2 and said VH(CLDN) comprises an amino acid sequence represented by SEQ ID NO: 8 and the VL(CLDN) comprises an amino acid sequence represented by SEQ ID NO: 15, wherein said VH(CD3) comprises an amino acid sequence represented by SEQ ID NO: 36 and the VL(CD3) comprises an amino acid sequence represented by SEQ ID NO: 37, wherein said binding agent comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 38, 39, 40 and 41.

2. The method of claim 1 , wherein the binding agent is a bispecific molecule.

3. The method of claim 2 , wherein the bispecific molecule is a bispecific antibody.

4. The method of claim 3 , wherein the bispecific antibody is a bispecific single chain antibody.

5. The method of claim 1 , wherein said first binding domain binds to an extracellular domain of said claudin.

6. The method of claim 1 , wherein said second binding domain binds to the epsilon-chain of CD3.

7. The method of claim 1 , wherein said CD3 is expressed on the surface of a T cell.

8. The method of claim 1 , wherein binding of said binding agent to CD3 on T cells results in proliferation and/or activation of said T cells, wherein said activated T cells preferably release cytotoxic factors, e.g. perforins and granzymes, and initiate cytolysis and apoptosis of cancer cells.

9. The method of claim 1 , wherein the binding agent is in the format of a bispecific single chain antibody that consists of two scFv molecules connected via a linker peptide.

Assignees

• Biontech Ag
• Ganymed Pharmaceuticals Ag
• Tron—Translationale Onkologie An Der Univ Der Johannes Gutenberg Univ Mainz Gemeinnutzige Gmb
• Tron Ggmbh
• Univ Der Johannes Gutenberg Univ Mainz

Inventors

• Sahin Ugur
• Tureci Ozlem
• Stadler Christiane
• Holland Julia
• Bahr-Mahmud Hayat
• Beissert Tim
• Plum Laura
• Le Gall Fabrice
• Jendretzki Arne
• Fiedler Markus

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/04

  specific for metastasis · CPC title

• C07K16/28 Primary

  against receptors, cell surface antigens or cell surface determinants · CPC title

• C07K2317/31

  multispecific · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title