Compositions and methods for immunomodulation in an organism

Patent metadata

Field	Value
Publication number	US-9371368-B2
Application number	US-201414567382-A
Country	US
Kind code	B2
Filing date	Dec 11, 2014
Priority date	May 17, 2005
Publication date	Jun 21, 2016
Grant date	Jun 21, 2016

Abstract

The present invention relates to a therapeutic polypeptide and methods for its creation and use for modulating an immune response in a host organism in need thereof. In particular, the invention relates to the administration to an organism in need thereof, of an effective amount of a pre-coupled polypeptide complex comprising a lymphokine polypeptide portion, for example IL-15 (SEQ ID NO: 5, 6), IL-2 (SEQ ID NO: 10, 12) or combinations of both, and an interleukin receptor polypeptide portion, for example IL-15Ra (SEQ ID NO: 7, 8), IL-2Ra (SEQ ID NO: 9, 11) or combinations of both, for augmenting the immune system in, for example, cancer, SCID, AIDS, or vaccination; or inhibiting the immune system in, for example, rheumatoid arthritis, or Lupus. The therapeutic complex of the invention surprisingly demonstrates increased half-life, and efficacy in vivo.

First claim

We claim:

1. A method for treating cancer, comprising administering to a human in need thereof a therapeutically effective amount of a composition, wherein the composition comprises a purified chimeric polypeptide in which an interleukin-15 (IL-15) polypeptide is linked to a soluble form of an interleukin-15 receptor alpha (IL-15Ra) polypeptide by a linker.

2. The method of claim 1 , wherein the IL-15 polypeptide is:
(i) (a) encoded by a nucleic acid that is at least 80% identical to SEQ ID NO: 2 over the entire length of SEQ ID NO: 2; or (b) at least 95% identical to the amino acid sequence of SEQ ID NO: 6 over the length of the mature form of SEQ ID NO: 6; and
(ii) capable of forming a complex with IL-15Ra polypeptide.

3. The method of claim 1 , wherein the IL-15 polypeptide has the amino acid sequence of SEQ ID NO: 6.

4. The method of claim 1 , wherein the soluble form of the IL-15Ra polypeptide is:
(i) a soluble form of an IL-15Ra polypeptide and the IL-15Ra polypeptide is (a) encoded by a nucleic acid that is at least 80% identical to SEQ ID NO: 4 over the entire length of SEQ ID NO: 4; or (b) at least 95% identical to the amino acid sequence of SEQ ID NO: 8 over the length of the mature form of SEQ ID NO: 8; and
(ii) capable of forming a complex with IL-15 polypeptide.

5. The method of claim 1 , wherein the soluble form of the IL-15Ra polypeptide:
(i) has the amino acid sequence of the extracellular domain of an IL-15Ra polypeptide and the IL-15Ra polypeptide is (a) encoded by a nucleic acid that is at least 80% identical to SEQ ID NO: 4 over the entire length of SEQ ID NO: 4; or (b) at least 95% identical to the amino acid sequence of SEQ ID NO: 8 over the length of the mature form of SEQ ID NO: 8; and
(ii) is capable of forming a complex with IL-15 polypeptide.

6. The method of claim 4 , wherein the IL-15Ra polypeptide has the amino acid sequence of SEQ ID NO: 8.

7. The method of claim 5 , wherein the IL-15Ra polypeptide has the amino acid sequence of SEQ ID NO: 8.

8. The method of claim 2 , wherein the soluble form of the IL-15Ra polypeptide is:
(i) a soluble form of an IL-15Ra polypeptide and the IL-15Ra polypeptide is (a) encoded by a nucleic acid that is at least 80% identical to SEQ ID NO: 4 over the entire length of SEQ ID NO: 4; or (b) at least 95% identical to the amino acid sequence of SEQ ID NO: 8 over the length of the mature form of SEQ ID NO: 8; and
(ii) capable of forming a complex with IL-15 polypeptide.

9. The method of claim 2 , wherein the soluble form of the IL-15Ra polypeptide:
(i) has the amino acid sequence of the extracellular domain of an IL-15Ra polypeptide and the IL-15Ra polypeptide is (a) encoded by a nucleic acid that is at least 80% identical to SEQ ID NO: 4 over the entire length of SEQ ID NO: 4; or (b) at least 95% identical to the amino acid sequence of SEQ ID NO: 8 over the length of the mature form of SEQ ID NO: 8; and
(ii) is capable of forming a complex with IL-15 polypeptide.

10. The method of claim 8 , wherein the IL-15Ra polypeptide has the amino acid sequence of SEQ ID NO: 8.

11. The method of claim 9 , wherein the IL-15Ra polypeptide has the amino acid sequence of SEQ ID NO: 8.

12. The method of claim 3 , wherein the soluble form of the IL-15Ra polypeptide is:
(i) a soluble form of an IL-15Ra polypeptide and the IL-15Ra polypeptide is (a) encoded by a nucleic acid that is at least 80% identical to SEQ ID NO: 4 over the entire length of SEQ ID NO: 4; or (b) at least 95% identical to the amino acid sequence of SEQ ID NO: 8 over the length of the mature form of SEQ ID NO: 8; and
(ii) capable of forming a complex with IL-15 polypeptide.

13. The method of claim 3 , wherein the soluble form of the IL-15Ra polypeptide:
(i) has the amino acid sequence of the extracellular domain of an IL-15Ra polypeptide and the IL-15Ra polypeptide is (a) encoded by a nucleic acid that is at least 80% identical to SEQ ID NO: 4 over the entire length of SEQ ID NO: 4; or (b) at least 95% identical to the amino acid sequence of SEQ ID NO: 8 over the length of the mature form of SEQ ID NO: 8; and
(ii) is capable of forming a complex with IL-15 polypeptide.

14. The method of claim 12 , wherein the IL-15Ra polypeptide has the amino acid sequence of SEQ ID NO: 8.

15. The method of claim 13 , wherein the IL-15Ra polypeptide has the amino acid sequence of SEQ ID NO: 8.

16. The method of claim 1 , wherein the composition is administered by a parenteral route.

17. The method of claim 1 , wherein the composition is administered by an intravenous route, subcutaneous route or intramuscular route.

18. The method of claim 1 , wherein the cancer is lymphoma.

19. The method of claim 1 , wherein the cancer is leukemia.

20. The method of claim 1 , wherein the cancer is prostate cancer, uterus cancer, liver cancer, melanoma, neoplasm, adenocarcinoma, lung cancer, kidney cancer or pancreatic cancer.

21. The method of claim 1 , wherein the human is lymphopenic.

22. The method of claim 1 , which further comprises administering another active ingredient to the human.

23. The method of claim 22 , wherein the active ingredient is anti-oncogenic.

Assignees

• Univ Connecticut

Inventors

• Lefrancois Leo
• Stoklasek Thomas A

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P35/00

  Antineoplastic agents · CPC title