Compositions and Methods for Immunomodulation in an Organism

Patent metadata

Field	Value
Publication number	US-2016347818-A1
Application number	US-201615156618-A
Country	US
Kind code	A1
Filing date	May 17, 2016
Priority date	May 17, 2005
Publication date	Dec 1, 2016
Grant date	—

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 polypeptide complex comprising an interleukin polypeptide or portion thereof, and an interleukin receptor polypeptide or portion thereof capable of binding said interleukin polypeptide, and wherein said interleukin polypeptide component and said interleukin receptor polypeptide component are pre-coupled.

2 . The polypeptide complex of claim 1 , wherein said interleukin polypeptide or portion thereof has a primary amino acid structure with at least 40% homology to a member selected from the group consisting of SEQ ID NO: 5, 6, 10, 12, and combinations of thereof.

3 . The polypeptide complex of claim 2 , wherein said interleukin polypeptide portion further comprises a signal peptide sequence on the amino terminus.

4 . The polypeptide complex of claim 1 , wherein said interleukin receptor or portion thereof comprises an antibody specific for the interleukin or a polypeptide with a primary amino acid structure with at least 40% homology to a member selected from the group consisting of SEQ ID NO: 7, 8, 9, 11, portions and combinations of thereof.

5 . The polypeptide complex of claim 4 , wherein the interleukin receptor component further comprises an antibody Fc portion.

6 . The polypeptide complex of claim 1 , wherein the pre-coupled complex has an in vivo half-life of at least one-hour.

7 . The polypeptide complex of claim 1 , wherein the complex comprises an interleukin polypeptide or portion thereof and an interleukin receptor polypeptide or portion thereof within a single polypeptide chain.

8 . A nucleic acid encoding the polypeptide complex of claim 1 , comprising a polynucleotide segment with at least 40% homology to a nucleic acid selected from the group consisting of SEQ ID NO: 1, 2, 14, 15, portions, and combinations thereof, contiguous with a polynucleotide segment that has at least 40% homology to a nucleic acid selected from the group consisting of SEQ ID NO: 3, 4, 13, 16, portions, and combinations thereof; wherein the interleukin polynucleotide, and interleukin receptor polynucleotide are capable of being expressed as a single polypeptide.

9 . The nucleic acid of claim 8 , further comprising a polynucleotide segment encoding an antibody Fc portion.

10 . An isolated host cell containing the nucleic acid molecule of claim 9 .

11 . A method of making a polypeptide complex, comprising the steps of:
providing an interleukin polypeptide or portion thereof; providing an interleukin receptor polypeptide or portion thereof capable of binding said interleukin; and combining and incubating said interleukin polypeptide and said interleukin receptor polypeptide for from about 1 minute to about 120 minutes, at from about 26° C. to about 40° C., in a suitable buffer having a pH from about 5.5 to about 8.5.

12 . The method of claim 11 , wherein said interleukin polypeptide or portion thereof has at least 40% homology to a member selected from the group consisting of SEQ ID NOs.: 5, 6, 10, 12, and combinations thereof, and wherein said interleukin receptor polypeptide or portion thereof has at least 40% homology to a member selected from the group consisting of SEQ ID NOs.: 7, 8, 9, 11, and combinations thereof.

13 . A method of increasing the activity of an immune cell comprising treating an immune ell with an effective amount of the polypeptide complex of claim 12 .

14 . A method of modulating immune function in an organism comprising the steps of:
providing the polypeptide complex of claim 12 ; and administering an effective amount of said polypeptide complex in a pharmaceutically acceptable form to an organism in need thereof.

15 . The method of claim 14 , wherein the polypeptide complex enhances immune function in said organism.

16 . The method of claim 14 , wherein the polypeptide complex inhibits immune function in said organism.

17 . The method of claim 12 , wherein the resulting polypeptide complex displays an in vivo half-life of greater than about 1 hour.

18 . The polypeptide complex of claim 12 , wherein the complex is contained in a kit comprising a suitable container, said polypeptide complex disposed therein, and instructions for its use.

19 . The polypeptide complex of claim 12 , wherein an effective amount of the complex is administered to an organism in need thereof at a dose which is equivalent to from about 0.1% to about 90% of the dose administered using interleukin alone.

20 . A method for modulating the immune response in an organism comprising administration of an effective amount of a pre-coupled polypeptide complex comprising an interleukin polypeptide portion derived from SEQ ID NO: 6, and an interleukin receptor polypeptide portion derived from SEQ ID NO: 7, wherein the interleukin receptor polypeptide portion derived from SEQ ID NO: 7 is capable of binding said interleukin polypeptide portion derived from SEQ ID NO: 6.

Assignees

• Stoklasek Thomas A
• Univ Connecticut

Inventors

• Lefrancois Leo
• Stoklasek Thomas A

Classifications

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/06

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

• A61P7/00

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

• A61P37/02

  Immunomodulators · CPC title