Robo1-Fc fusion protein and use thereof for treating tumours

Patent metadata

Field	Value
Publication number	US-9493529-B2
Application number	US-201113641012-A
Country	US
Kind code	B2
Filing date	Apr 8, 2011
Priority date	Apr 14, 2010
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

Abstract

The present invention relates to a Robo1-Fc recombinant protein and to the use thereof for treating diseases in which a Slit protein is overexpressed, in particular cancer. The invention also relates to a composition including such a recombinant protein. Another aspect of the invention involves using a Robo1-Fc molecule as a diagnostic tool for detecting the overexpression of a molecule belonging to the Slit family in a patient.

First claim

We claim:

1. A homogeneous composition of Robo-Fc recombinant protein comprising the extracellular region of a Robo1 protein, a linker and an immunoglobulin Fc domain,
wherein said extracellular region of the Robo1 protein consists of the Ig1 and Ig2 immunoglobulin domains corresponding to amino acids 22-220 of SEQ ID NO: 2,
wherein the immunoglobulin Fc domain is from human immunoglobulin G4 and comprises S241P and L248E mutations (Kabat numbering), and wherein the lysine located in the C-terminal position is absent.

2. The homogeneous composition of Robo-Fc recombinant protein according to claim 1 , wherein the sequence has at least 80% identity with the sequence of SEQ ID NO: 4, SEQ ID NO: 6 or SEQ ID NO: 24.

3. A pharmaceutical composition comprising the homogeneous composition of Robo-Fc recombinant protein of claim 1 .

4. A method for treating a cancer associated with overexpression of a protein of the Slit family comprising administering to a subject in need thereof the pharmaceutical composition of claim 3 .

5. The method of claim 4 , wherein the cancer is lung cancer or lung metastases.

6. The pharmaceutical composition according to claim 3 further comprising at least one excipient.

7. A method for detecting overexpression of a molecule of the Slit family in a patient comprising contacting a biological sample from the patient with the homogeneous composition of Robo-Fc recombinant protein of claim 1 .

8. The homogeneous composition of Robo-Fc recombinant protein according to claim 1 , which is produced by transfection of expression plasmid encoding a protein having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6 or SEQ ID NO: 24 into CHO cell, recovery in culture supernatant and purification.

9. The homogeneous composition of Robo-Fc recombinant protein according to claim 1 , wherein the Robo-Fc recombinant protein consists of amino acids 22 to 454 of SEQ ID NO: 4.

10. The homogeneous composition of Robo-Fc recombinant protein according to claim 1 , wherein the Robo-Fc recombinant protein consists of amino acids 22 to 453 of SEQ ID NO: 6.

11. The homogeneous composition of Robo-Fc recombinant protein according to claim 1 , wherein the Robo-Fc recombinant protein consists of amino acids 21 to 453 of SEQ ID NO: 24.

Assignees

• Blanche Francis
• Cameron Beatrice
• Dabdoubi Tarik
• Dol-Gleizes Frederique
• Fons Pierre
• Prades Catherine
• Herault Jean-Pascal
• Sanofi Sa

Inventors

• Blanche Francis
• Cameron Beatrice
• Dabdoubi Tarik
• Dol-Gleizes Frederique
• Fons Pierre
• Prades Catherine
• Herault Jean-Pascal

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• C12N15/09

  Recombinant DNA-technology · CPC title

• C07K14/475 Primary

  Growth factors; Growth regulators · CPC title