Multimeric IL-15 soluble fusion molecules and methods of making and using same

Patent metadata

Field	Value
Publication number	US-10150805-B2
Application number	US-201615083998-A
Country	US
Kind code	B2
Filing date	Mar 29, 2016
Priority date	Sep 21, 2010
Publication date	Dec 11, 2018
Grant date	Dec 11, 2018

Abstract

The present invention features compositions and methods featuring ALT-803, a complex of an interleukin-15 (IL-15) superagonist mutant and a dimeric IL-15 receptor α/Fc fusion protein useful for enhancing an immune response against a neoplasia (e.g., multiple myeloma, melanoma, lymphoma) or a viral infection (e.g., human immunodeficiency virus).

First claim

What is claimed is:

1. An IL-15 receptor fusion polypeptide comprising an IL-15 receptor alpha sushi-binding domain fused to an Fc domain (IL-15RaSu/Fc) and a variant interleukin-15 polypeptide comprising an N72D mutation (IL-15N72D) complex (IL-15N72D:IL-15RaSu/Fc; Alt-803) comprising a dimeric IL-15RaSu/Fc and two IL-15N72D molecules.

2. The polypeptide of claim 1 , wherein the IL-15RaSu/Fc comprises SEQ ID NO: 1.

3. The polypeptide of claim 2 , wherein amino acids 1-65 of SEQ ID NO: 1 comprise IL-15RaSu.

4. The polypeptide of claim 3 , wherein amino acids 66-297 of SEQ ID NO: 1 comprise IgG1 CH2-CH3 (Fc domain).

5. The polypeptide of claim 2 , wherein amino acids 20-84 of SEQ ID NO: 4 comprise IL-15RaSu.

6. The polypeptide of claim 5 , wherein amino acids 85-316 comprise IgG1 CH2-CH3 (Fc domain).

7. The polypeptide of claim 1 , wherein the IL-15N72D comprises SEQ ID NO: 2.

8. A nucleic acid sequence encoding the polypeptide of claim 1 .

9. A nucleic acid sequence encoding an IL-15 receptor fusion polypeptide comprising an IL-15RaSu/Fc and an IL-15N72D complex (IL-15N72D:IL-15RaSu/Fc; Alt-803), wherein the nucleic acid sequence encoding IL-15RaSu/Fc comprises SEQ ID NO: 57, and wherein the nucleic acid sequence encoding IL-15N72D comprises SEQ ID NO: 56.

10. The polypeptide of claim 1 , wherein the IL-15RaSu/Fc comprises SEQ ID NO: 4.

11. The polypeptide of claim 1 , wherein the IL-15N72D comprises SEQ ID NO: 3.

12. A nucleic acid sequence encoding the polypeptide of claim 2 .

13. A nucleic acid sequence encoding the polypeptide of claim 3 .

14. A nucleic acid sequence encoding the polypeptide of claim 4 .

15. A nucleic acid sequence encoding the polypeptide of claim 5 .

16. A nucleic acid sequence encoding the polypeptide of claim 10 .

17. A nucleic acid sequence encoding the polypeptide of claim 11 .

18. The nucleic acid sequence of claim 9 , wherein the nucleic acid sequence encoding IL-15N72D comprises nucleic acids 61 to 402 of SEQ ID NO: 56.

19. The nucleic acid sequence of claim 9 , wherein the nucleic acid sequence encoding the IL-15RaSu/Fc comprises nucleic acids 58 to 948 SEQ ID NO: 57.

20. The polypeptide of claim 11 , wherein the IL-15N72D comprises amino acids 21 to 134 of SEQ ID NO: 3.

Assignees

• Altor Bioscience Corp
• Altor Bioscience Llc

Inventors

• Wong Hing C
• Rhode Peter
• Liu Bai
• Zhu Xiaoyun
• Han Kai-Ping

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P43/00

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

• A61P31/18

  for HIV · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P37/02

  Immunomodulators · CPC title