Il-15 and il-15r\alpha sushi domain based immunocytokines

Patent metadata

Field	Value
Publication number	US-2024083963-A1
Application number	US-202318352998-A
Country	US
Kind code	A1
Filing date	Jul 14, 2023
Priority date	Jun 24, 2011
Publication date	Mar 14, 2024
Grant date	—

Abstract

The present invention relates to an immunocytokine comprising (a) a conjugate, and (b) an antibody or a fragment thereof directly or indirectly linked by covalence to said conjugate, wherein said conjugate comprises (i) a polypeptide comprising the amino acid sequence of the interleukin 15 or derivatives thereof, and (ii) a polypeptide comprising the amino acid sequence of the sushi domain of the interleukin 15R alpha (IL-15Rα) or derivatives thereof; and uses thereof.

First claim

1 - 16 . (canceled)

17 . An immunocytokine comprising:
a) a conjugate, and b) an antibody directly or indirectly linked by covalence to said conjugate, wherein said conjugate comprises:
(i) a polypeptide comprising the amino acid sequence of the interleukin 15 or derivatives thereof having at least 92.5% sequence identity with the amino acid sequence of SEQ ID NO:3, and
(ii) a polypeptide comprising the amino acid sequence of the sushi domain of the IL-15Rα or derivatives thereof having at least 92% sequence identity with the amino acid sequence of SEQ ID NO: 8 or SEQ IDNO: 9,

wherein said antibody is directed against a tumor antigen or a tumor neovascularization antigen.

18 . The immunocytokine of claim 1 , wherein the polypeptides i) and ii) of the conjugate are covalently linked in a fusion protein.

19 . The immunocytokine of claim 18 , wherein the amino acid sequence of the conjugate and the amino acid sequence of the antibody are not separated by any linker amino acid sequence.

20 . The immunocytokine of claim 18 , wherein the amino acid sequence of the conjugate and the amino acid sequence of the antibody are separated by a second linker amino acid sequence.

21 . The immunocytokine of claim 17 , wherein said interleukin 15 has the amino acid sequence SEQ ID NO: 3.

22 . The immunocytokine of claim 17 , wherein sushi domain of IL-15Rα has the amino acid sequence SEQ ID NO: 8 or SEQ ID NO: 9.

23 . The immunocytokine of claim 17 , wherein the polypeptide (ii) comprising the amino acid sequence of the sushi domain of the 1L-15Rα or derivatives thereof has the amino acid sequence SEQ ID NO: 12.

24 . The immunocytokine of claim 18 , wherein said conjugate comprises the amino acid sequence of the interleukin 15 or derivatives thereof in a C-terminal position relative to the amino acid sequence of the sushi domain of the IL-15Rα or derivatives thereof.

25 . The immunocytokine of claim 18 , wherein the amino acid sequence of the interleukin 15 or derivatives thereof and the amino acid sequence of the sushi domain of the 1L-15Rα or derivatives are separated by a first linker amino acid sequence.

26 . The immunocytokine of claim 17 , wherein the antigen related to tumor neovascularization is selected from the group consisting of the EDA and the EDB domains of fibronectin, Endosalin/TEM1, Endoglin/105, PSMA and B7-H4.

27 . The immunocytokine of claim 17 , wherein the antigen related to the tumoral antigen is selected from the group consisting of CD-20, CEA, EGFR, GD2, EPCAM, MUC1, PSMA, CD-19, GD3, GM1, CAIX, GD2-O-acetylated and HER2.

28 . The immunocytokine of claim 17 , wherein the amino acid sequence of the conjugate is in a C-terminal position relative to the amino acid sequence of the antibody.

29 . A pharmaceutical composition comprising the immunocytokine as defined in claim 17 eventually associated with a pharmaceutically acceptable carrier.

30 . The pharmaceutical composition of claim 29 , wherein said pharmaceutical composition is for treating cancer in a subject, preferably by an administration by injection at a dose of 2.5 mg/kg of subject or less.

Assignees

• Cytune Pharma
• Inst Nat Sante Rech Med

Inventors

• Morisseau Sebastien Daniel
• Teppaz Geraldine
• Jacques Yannick Laurent Joseph
• Robert Bruno Gilbert Marc
• De Martynoff Guy Luc Michel
• Béchard David

Classifications

• A61K2039/54

  characterised by the route of administration · CPC title

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title

• A61K38/2086 Primary

  IL-13 to IL-16 · CPC title

• C07K14/5443 Primary

  IL-15 · CPC title

• C07K14/7155

  for interleukins [IL] · CPC title