Targeted TGFβ inhibitors

Patent metadata

Field	Value
Publication number	US-9676863-B2
Application number	US-201514618454-A
Country	US
Kind code	B2
Filing date	Feb 10, 2015
Priority date	Feb 10, 2014
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

This invention relates generally to bifunctional molecules including (a) a TGFβRII or fragment thereof capable of binding TGFβ and (b) an antibody, or antigen binding fragment thereof, that binds to an immune checkpoint protein, such as Programmed Death Ligand 1 (PD-L1), uses of such molecules (e.g., for treating cancer), and methods of making such molecules.

First claim

What is claimed is:

1. A protein comprising:
a first polypeptide comprising:
a) at least a variable region of a heavy chain of an antibody that binds human protein Programmed Death Ligand 1 (PD-L1); and
b) human Transforming Growth Factor β Receptor II (TGFβRII), or a fragment thereof capable of binding Transforming Growth Factor β (TGFβ); and

a second polypeptide comprising at least a variable region of a light chain of an antibody that binds PD-L1,
wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO: 3,
wherein the second polypeptide comprises the amino acid sequence of SEQ ID NO: 1, and wherein the heavy chain of the first polypeptide and the light chain of the second polypeptide, when combined, form an antigen binding site that binds PD-L1.

2. The protein of claim 1 , comprising two polypeptides each having an amino acid sequence consisting of the amino acid sequence of SEQ ID NO: 3, and two additional polypeptides each having an amino acid sequence consisting of the amino acid sequence of SEQ ID NO: 1.

3. A nucleic acid comprising a first nucleotide sequence encoding the first polypeptide according to claim 1 , and a second nucleotide sequence encoding the second polypeptide according to claim 1 .

4. An isolated cell comprising the nucleic acid of claim 3 .

5. A method of producing a protein comprising a) TGFβRII, or a fragment thereof capable of binding TGFβ, and b) an antibody, or an antigen-binding fragment thereof, that binds human protein Programmed Death Ligand 1 (PD-L1), the method comprising maintaining a cell according to claim 4 under conditions permitting expression of the protein.

6. The method of claim 5 , further comprising harvesting the protein.

Assignees

• Merck Patent Gmbh

Inventors

• Lo Kin-Ming

Classifications

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P43/00

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

• A61P5/14

  of the thyroid hormones, e.g. T3, T4 · CPC title