Cytokine-based fusion proteins for treatment of immune disorders

Patent metadata

Field	Value
Publication number	US-9745361-B2
Application number	US-201414530270-A
Country	US
Kind code	B2
Filing date	Oct 31, 2014
Priority date	Oct 31, 2006
Publication date	Aug 29, 2017
Grant date	Aug 29, 2017

Abstract

The present invention provides fusion proteins including an autoimmune antigen, an allergen antigen or an alloantigen, and an anti-inflammatory cytokine. Compositions and methods including the fusion proteins are also provided.

First claim

That which is claimed:

1. A fusion protein comprising:
an autoimmune antigen selected from the group consisting of a myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG) or myelin-associated oligodendrocytic basic protein; and
an anti-inflammatory cytokine selected from the group consisting of an interleukin, interleukin receptor antagonist, interferon-beta (IFN-β) and transforming growth factor-beta (TGF-β).

2. The fusion protein of claim 1 , wherein the autoimmune antigen comprises an encephalitogenic determinant of the protein.

3. The fusion protein of claim 2 , wherein the encephalitogenic determinant of the myelin basic protein comprises the amino acid sequence of SEQ ID NO:2.

4. The fusion protein of claim 1 , wherein the interleukin is interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin 13 (IL-13), or interleukin-16 (IL-16)) and the interleukin receptor antagonist is interleukin-1RA (IL-1RA).

5. The fusion protein of claim 1 , wherein the autoimmune antigen is covalently linked directly or through a linking moiety.

6. The fusion protein of claim 1 , wherein the autoimmune antigen is a myelin basic protein.

7. The fusion protein of claim 1 , wherein the autoimmune antigen is a proteolipid protein.

8. The fusion protein of claim 1 , wherein the autoimmune antigen is a myelin oligodendrocyte glycoprotein.

9. An isolated nucleic acid encoding the fusion protein of claim 1 .

10. A vector comprising the isolated nucleic acid of claim 9 .

11. An isolated host cell comprising the vector of claim 10 .

12. A method of making a fusion protein comprising:
(a) culturing an isolated host cell of claim 11 ; and
(b) collecting the encoded fusion protein from said culture.

13. A method of treating multiple sclerosis in a subject comprising administering to the subject an effective amount of the fusion protein of claim 1 .

14. The method of claim 13 , wherein the autoimmune antigen is a myelin basic protein.

15. The method of claim 14 , wherein an encephalitogenic determinant of the myelin basic protein comprises the amino acid sequence of SEQ ID NO:2.

16. A composition comprising:
(a) at least one fusion protein comprising (i) an autoimmune antigen selected from the group consisting of a myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG) or myelin-associated oligodendrocytic basic protein, and (ii) an anti-inflammatory cytokine selected from the group consisting of an interleukin, interleukin receptor antagonist, interferon-beta (IFN-β) and transforming growth factor-beta (TGF-β); and
(b) a pharmaceutically acceptable carrier, excipient or diluent, and when two or more fusion proteins are present, at least one fusion protein comprises an anti-inflammatory cytokine that is different from the anti-inflammatory cytokine of least one other fusion protein.

17. A kit comprising one or more containers having pharmaceutical dosage units comprising an effective amount of a fusion protein, wherein the container is packaged with optional instructions for the use thereof; said fusion protein comprising an autoimmune antigen selected from the group consisting of a myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG) or myelin-associated oligodendrocytic basic protein; and an anti inflammatory cytokine selected from the group consisting of an interleukin, interleukin receptor antagonist, interferon-beta (IFN-β) and transforming growth factor-beta (TGF-β).

Assignees

• Univ East Carolina

Inventors

• Mannie Mark D

Classifications

• A61P37/06

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

• A61K38/2086

  IL-13 to IL-16 · CPC title

• C12N15/62

  DNA sequences coding for fusion proteins · CPC title

• C07K2319/40

  containing a tag for immunodetection, or an epitope for immunisation · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title