Cell expressing complexes of IL-15 and IL-15Ralpha

Inventors: George N. Pavlakis (Rockville, MD); John N. Vournakis (Charleston, SC); Barbara K. Felber (Rockville, MD); Sergio Finkielsztein (Newton, MA)

Assignees: The United States of America, as Represented by the Secretary, Department of Health and Human Services; Novartis AG

A61K38/2086 A61K38/1793 A61K39/0011 A61K2039/5152 A61K2039/5156 A61K2039/55527

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Quick Facts

Patent No.: US 9,931,377
App. No.: 12/666,052
Granted: Apr 3, 2018
Kind: B2

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Abstract

The present invention relates to agents that modulate interleukin-15 (“IL-15”) signal transduction or function (“Therapeutic Agents”) and the use ol″ those agents to modulate immune function. The Therapeutic Agents target the interaction between IL-15 and its receptor and modulate IL-15-induced signal transduction. The Therapeutic Agents may be formulated with polymers, such as poly-β-1-♦4-N-acetylglucosamine. for administration to a human subject to modulate IL-15-mediated immune function.

Claims (23)

1. An isolated cell that recombinantly expresses any one of: (i) human IL-15 and a soluble form of human IL-15Ra at least 95% identical to the amino acid sequence comprising amino acid residues 31-267 of SEQ ID NO:3, (ii) a complex comprising human IL-15 and a soluble form of human IL-15Ra, wherein the human IL-15Ra is at least 95% identical to the amino acid sequence comprising amino acid residues 31-267 of SEQ ID NO:3, wherein the cell expresses at least 0.15 pg of human IL-15 per day when cultured in serum-free media.

2. The cell of claim 1 , wherein the human IL-15 is at least 95% identical to the amino acid sequence comprising amino acid residues 49 to 162 of SEQ ID NO:1.

3. The cell of claim 1 , wherein the human IL-15 comprises the amino acid sequence of amino acid residues 49 to 162 of SEQ ID NO:1.

4. The cell of claim 1 , wherein the human IL-15Ra comprises the amino acid sequence of amino acid residues 31 to 267 of SEQ ID NO:3.

5. The cell of claim 1 , wherein the soluble form of human IL-15Ra is at least 95% identical to the amino acid sequence comprising amino acid residues 31 to 205 of SEQ ID NO: 4.

6. The cell of claim 1 , wherein: (I) the human IL-15 is at least 95% identical to the amino acid sequence comprising amino acid residues 49 to 162 of SEQ ID NO:1; (II) the human IL-15Ra is at least 95% identical to the amino acid sequence comprising amino acid residues 31 to 267 of SEQ ID NO:3.

7. The cell of claim 1 , wherein: (I) the human IL-15 is at least 95% identical to the amino acid sequence comprising amino acid residues 49 to 162 of SEQ ID NO:1; (II) the soluble form of human IL-15Ra is at least 95% identical to the amino acid sequence comprising amino acid residues 31 to 205 of SEQ ID NO:4.

8. The cell of claim 1 , wherein: (I) the human IL-15 consists of the amino acid sequence of amino acid residues 49 to 162 of SEQ ID NO:1; (II) the human IL-15Ra consists of the amino acid sequence of amino acid residues 31 to 267 of SEQ ID NO:3.

9. The cell of claim 1 , wherein the cell is an irradiated cancer cell.

10. The cell of claim 1 , wherein the cell is a mammalian cell line.

11. The cell of claim 1 , wherein the cell is from a 293H, 293 or CHO cell line.

12. The cell of claim 1 , wherein the cell expresses at least 0.6 pg of human IL-15 per day.

13. The cell of claim 1 , wherein the cell expresses at least 1 pg of human IL-15 per day.

14. The cell of claim 1 , wherein the cell expresses up to 2 pg of human IL-15 per day.

15. An isolated cell that recombinantly expresses a complex comprising human IL-15 and human IL-15Ra from a codon-optimized nucleic acid sequence encoding human IL-15 and a codon-optimized nucleic acid sequence encoding human IL-15Ra, wherein the human IL-15Ra is at least 95% identical to amino acid residues 31-267 of SEQ ID NO:14 or 31-205 of SEQ ID NO:16, wherein the cell expresses at least 0.15 pg of human IL-15 per day when cultured in serum-free media.

16. The isolated cell of claim 15 , wherein the human IL-15 comprises amino acid residues 30 to 162 of SEQ ID NO:10; and the human IL15Ra comprises amino acid residues 31 to 267 of SEQ ID NO:14.

17. The isolated cell of claim 15 , wherein the human IL-15 comprises amino acid residues 30 to 162 of SEQ ID NO:10; and the human IL15Ra comprises amino acid residues 31 to 205 of SEQ ID NO:16.

18. The isolated cell of claim 15 , wherein the human IL-15 comprises amino acid residues 36 to 149 of SEQ ID NO:12; and the human IL15Ra comprises amino acid residues 31 to 267 of SEQ ID NO:14.

19. The isolated cell of claim 15 , wherein the human IL-15 comprises amino acid residues 36 to 149 of SEQ ID NO:12; and the human IL15Ra comprises amino acid residues 31 to 205 of SEQ ID NO:16.

20. The isolated cell of claim 15 , wherein the human IL-15 comprises amino acid residues 18 to 131 of SEQ ID NO:18; and the human IL15Ra comprises amino acid residues 31 to 267 of SEQ ID NO:14.

21. The isolated cell of claim 15 , wherein the human IL-15 comprises amino acid residues 18 to 131 of SEQ ID NO:18; and the human IL15Ra comprises amino acid residues 31 to 205 of SEQ ID NO:16.

22. The cell of claim 15 , wherein the cell is a mammalian cell line.

23. The cell of claim 15 , wherein the cell is from a 293H, 293 or CHO cell line.

Assignments (4)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 28, 2016

From: ADMUNE THERAPEUTICS LLC

To: NOVARTIS AG

Reel/Frame 040163/0257 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 8, 2013

From: MARINE POLYMER TECHNOLOGIES, INC.

To: ADMUNE THERAPEUTICS. LLC

Reel/Frame 031569/0327 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 29, 2011