Anti-cancer fusion polypeptide

Patent metadata

Field	Value
Publication number	US-10865250-B2
Application number	US-201615571561-A
Country	US
Kind code	B2
Filing date	May 4, 2016
Priority date	May 4, 2015
Publication date	Dec 15, 2020
Grant date	Dec 15, 2020

Abstract

The disclosure provides a fusion polypeptide specific for both CD137 and HER2/neu, which fusion polypeptide can be useful for directing CD137 clustering and activation to HER2/neu-positive tumor cells. Such fusion polypeptide can be used in many pharmaceutical applications, for example, as anti-cancer agents and/or immune modulators for the treatment or prevention of human diseases such as a variety of tumors. The present disclosure also concerns methods of making the fusion polypeptide described herein as well as compositions comprising such fusion polypeptide. The present disclosure further relates to nucleic acid molecules encoding such fusion polypeptide and to methods for generation of such fusion polypeptide and nucleic acid molecules. In addition, the application discloses therapeutic and/or diagnostic uses of such fusion polypeptide as well as compositions comprising one or more of such fusion polypeptides.

First claim

The invention claimed is:

1. A fusion polypeptide that is capable of simultaneously binding both CD137 and HER2/neu, wherein the fusion polypeptide comprises at least two subunits, wherein the first subunit comprises an immunoglobulin, which first binding domain has binding specificity for HER2/neu, and wherein the second subunit comprises a lipocalin mutein having binding specificity for CD137, wherein the fusion polypeptide comprises the amino acid sequences shown in SEQ ID NOs: 9 and 10.

2. The fusion polypeptide of claim 1 , wherein the fusion polypeptide is capable of binding CD137 with an EC 50 value comparable to or lower than the EC 50 value of the lipocalin mutein specific for CD137 included in the fusion polypeptide.

3. The fusion polypeptide of claim 1 , wherein the fusion polypeptide is capable of binding CD137 with an EC 50 value of about 1 nM or lower.

4. The fusion polypeptide of claim 1 , wherein the fusion polypeptide is capable of binding HER2/neu with an EC 50 value comparable to or lower than the EC 50 value of the immunoglobulin specific for HER2/neu included in such fusion polypeptide.

5. The fusion polypeptide of claim 1 , wherein the fusion polypeptide is capable of binding HER2/neu with an EC 50 value of about 1 nM.

6. The fusion polypeptide of claim 1 , wherein the fusion polypeptide is capable of simultaneously binding CD137 and HER2/neu with EC 50 values of about 4 nM or lower.

7. The fusion polypeptide of claim 1 , wherein the fusion polypeptide is capable of co-stimulating T-cell responses.

8. The fusion polypeptide of claim 1 , wherein the fusion polypeptide is capable of inducing IL-2 secretion and T cell proliferation.

Assignees

• Pieris Pharmaceuticals Gmbh

Inventors

• Hinner Marlon
• Rothe Christine
• Olwill Shane
• Bel Aiba Rachida Siham
• Moebius Ulrich
• Schlosser Corinna
• Jaquin Thomas Jean

Classifications

• C07K2319/70

  containing domain for protein-protein interaction · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K2318/20

  Antigen-binding scaffold molecules wherein the scaffold is not an immunoglobulin variable region or antibody mimetics · CPC title

• C07K2317/73

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

• C07K2317/52

  Constant or Fc region; Isotype · CPC title