Il-15 and il-15raplha sushi domain based modulokines

Patent metadata

Field	Value
Publication number	US-2016175459-A1
Application number	US-201414910475-A
Country	US
Kind code	A1
Filing date	Aug 8, 2014
Priority date	Aug 8, 2013
Publication date	Jun 23, 2016
Grant date	—

Abstract

The present invention relates to an immunocytokine comprising (a) a conjugate, and (b) an immunomodulatory 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 a polypeptide comprising the amino acid sequence of the sushi domain of the IL-15Rα or derivatives thereof; and uses thereof.

First claim

1 . An immunocytokine comprising:
a) a conjugate, and b) an immunomodulatory 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 IL-15Rα or derivatives thereof.

2 . The immunocytokine of claim 1 , wherein said immunomodulatory antibody stimulates a co-stimulatory receptor and is selected from the group consisting of CD40 agonists, CD137 agonists, CD134 agonists and TNFRSF18 agonists.

3 . The immunocytokine of claim 1 , wherein said immunomodulatory antibody inhibits an immunosuppressive receptor and is selected from the group consisting of CTL-A4 antagonists, inhibitory KIRs antagonists, BTLA antagonists, LAG3 antagonists, HAVCR2 antagonists, ADORA2A antagonists and PD-1 antagonists.

4 . The immunocytokine of claim 3 , wherein said immunomodulatory antibody inhibiting an immunosuppressive receptor is selected from CTL-A4 antagonists.

5 . The immunocytokine of claim 3 , wherein said immunomodulatory antibody inhibiting an immunosuppressive receptors is selected from inhibitory KIRs antagonists.

6 . The immunocytokine of claim 3 , wherein said immunomodulatory antibody inhibiting an immunosuppressive receptors is selected from PD-1 antagonists.

7 . The immunocytokine of claim 1 , wherein
a) the polypeptides i) and ii) of the conjugate are covalently linked in a fusion protein; and b) said conjugate and the antibody or fragment thereof are covalently linked in a fusion protein.

8 . The immunocytokine of claim 1 , wherein said interleukin 15 has the amino acid sequence SEQ ID no 1.

9 . The immunocytokine of claim 1 , wherein sushi domain of IL-15Rα has the amino acid sequence SEQ ID no 4.

10 . The immunocytokine of claim 1 , wherein the polypeptide (ii) comprising the amino acid sequence of the sushi domain of the IL-15Rα or derivatives thereof has the amino acid sequence SEQ ID no 12.

11 . The immunocytokine of claim 7 , 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, and wherein the amino acid sequence of the conjugate is in a C terminal position relative to the amino acid sequence of the antibody or fragment thereof

12 . A nucleic acid encoding for an immunocytokine as defined in claim 1 .

13 . A vector comprising a nucleic acid as defined in claim 12 .

14 . A host cell genetically engineered with the nucleic acid of claim 12 .

15 . A pharmaceutical composition comprising the immunocytokine as defined in claim 1 , associated with a pharmaceutically acceptable carrier.

16 . The pharmaceutical composition of claim 15 , wherein said pharmaceutical composition is for treating cancer in a subject.

17 . A host cell genetically engineered with the vector of claim 13 .

18 . The host cell of claim 14 , wherein said host cell is an animal cell.

19 . A pharmaceutical composition comprising the nucleic acid of claim 12 associated with a pharmaceutically acceptable carrier.

20 . A pharmaceutical composition comprising the vector of claim 13 associated with a pharmaceutically acceptable carrier.

Assignees

• Cytune Pharma
• Univ Paris Descartes
• Assist Publ Hopitaux De Paris

Inventors

• Gey Alain
• Tartour Eric
• Bechard David

Classifications

• A61P43/00

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61K38/2086 Primary

  IL-13 to IL-16 · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K16/2818

  against CD28 or CD152 · CPC title