Modulation of SOCS expression in therapeutic regimens

• US 20050084477A1
• Filed: 09/08/2004
• Published: 04/21/2005
• Est. Priority Date: 10/21/2003
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Gulati, Poonam S., Van Antwerp, William P.
• Granted Patent: US 8,034,764 B2
• Time in Patent Office: Days
• US Class Current: 424/85.100
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A method is provided for treating conditions that are susceptible of treatment with a cytokine wherein certain physiological processes normally associated with cytokine administration (e.g. the induction of SOCS 1 and/or SOCS 3) are diminished or eliminated. The method comprises continuously administering a controlled dose of a cytokine to an individual afflicted with a condition susceptible of treatment with the cytokine.

Claims

1. A method of inhibiting the induction of mRNA encoding SOCS 1 (SEQ ID NO:

1) or SOCS 3 (SEQ ID NO;

     3) polypeptide in a human cell exposed to a therapeutically effective amount of a cytokine capable of inducing the SOCS 1 or SOCS 3 mRNA, the method comprising the steps of;

(a) determining the minimal amount of cytokine that will induce mRNA encoding SOCS 1 or SOCS 3 in the human cell; and

(b) exposing the human cell to an therapeutically effective amount of a SOCS inducing cytokine that is less than the amount determined in step (a) so that the induction of mRNA encoding SOCS 1 or SOCS 3 in the human cell is inhibited.

2. The method of claim 1, wherein the cytokine capable of inducing the SOCS 1 or SOCS 3 mRNA is combined with a pharmaceutically acceptable carrier.

3. The method of claim 1, wherein the cytokine capable of inducing the SOCS 1 or SOCS 3 mRNA is parenterally administered to a human.

4. The method of claim 3, wherein the parenterally administered SOCS inducing cytokine is insulin, insulin-like growth factor, alpha interferon, beta interferon, gamma interferon, growth hormone, prolactin, interleukin-2, interleukin-4, interleukin-6, interleukin-7, interleukin-10, interleukin-12, LIF, growth hormone, TPO, prolactin, stem cell factor, erythropoietin or tumor necrosis factor.

5. The method of claim 1, wherein the human cell is in a patient and the cytokine is administered to the patient via continuous infusion.

6. The method of claim 5, wherein the cytokine is administered to the patient by a continuous infusion pump.

7. The method of claim 5, wherein the amount of cytokine administered is controlled to be 80%, 85%, 90%, or 95% of the threshold amount that is necessary to generate an induction of mRNA encoding SOCS 1 (SEQ ID NO:

1) or SOCS 3 (SEQ ID NO;

     3) lasting more than 4, 8, 12 or 24 hours.

8. The method of claim 1, wherein the SOCS polypeptide is SOCS 1.

9. The method of claim 1, wherein the SOCS polypeptide is SOCS 3.

10. A method of inhibiting the induction of mRNA encoding SOCS 1 (SEQ ID NO:

1) or SOCS 3 (SEQ ID NO;

     3) polypeptide in a human cell exposed to a therapeutically effective amount of a cytokine capable of inducing the SOCS 1 or SOCS 3 mRNA, the method comprising the steps of;

(a) determining the minimal amount of cytokine that will induce mRNA encoding SOCS 1 or SOCS 3 in the human cell, wherein the induction is not a transient increase in mRNA encoding SOCS 1 or SOCS 3; and

(b) exposing the human cell to an therapeutically effective amount of a SOCS inducing cytokine that is less than the amount determined in step (a) so that the induction of mRNA encoding SOCS 1 or SOCS 3 in the human cell is inhibited.

11. The method of claim 10, wherein the cytokine capable of inducing the SOCS 1 or SOCS 3 mRNA is combined with a pharmaceutically acceptable carrier.

12. The method of claim 10, wherein the human cell is in a patient and the cytokine is administered to the patient via continuous infusion.

13. The method of claim 10, wherein the SOCS inducing cytokine is insulin, insulin-like growth factor, alpha interferon, beta interferon, gamma interferon, growth hormone, prolactin, interleukin-2, interleukin-4, interleukin-6, interleukin-7, interleukin-10, interleukin-12, LIF, growth hormone, thrombopoietin, prolactin, stem cell factor, erythropoietin or tumor necrosis factor.

14. A method of controlling the biological activity of SOCS 1 (SEQ ID NO:

1) or SOCS 3 (SEQ ID NO;

     3) in a human cell exposed to a therapeutically effective amount of a cytokine capable of inducing SOCS 1 or SOCS 3 biological activity, the method comprising the steps of;

(a) determining the minimal amount of SOCS inducing cytokine that will induce sustained SOCS 1 or SOCS 3 biological activity in the human cell; and

(b) exposing the human cell to an therapeutically effective amount of a SOCS inducing cytokine that is less than the amount determined in step (a) so that the induction of SOCS 1 or SOCS 3 biological activity in the human cell is controlled.

15. The method of claim 14, wherein the cytokine capable of inducing the SOCS 1 or SOCS 3 biological activity is combined with a pharmaceutically acceptable carrier.

16. The method of claim 14, wherein the human cell is in a patient and the cytokine is administered to the patient via continuous infusion.

17. The method of claim 14, wherein the SOCS inducing cytokine is insulin, insulin-like growth factor, alpha interferon, beta interferon, gamma interferon, growth hormone, prolactin, interleukin-2, interleukin-4, interleukin-6, interleukin-7, interleukin-10, interleukin-12, LIF, growth hormone, thrombopoietin, prolactin, stem cell factor, erythropoietin or tumor necrosis factor.

18. The method of claim 14, wherein the minimal amount of cytokine that induce SOCS 1 or SOCS 3 biological activity in the human cell is determined by an assay which examines the phosphorylation of tyrosine residues on STAT1.

19. The method of claim 14, wherein the human cell is in a patient and the cytokine is administered to the patient via a continuous infusion pump.

20. The method of claim 14, wherein the human cell is in a patient infected with a hepatitis virus and the cytokine is an interferon which is administered to the patient via continuous infusion.

21. The method of claim 20, wherein the method results in at least a 90% or 95% decrease in viral levels in the patient.