CONTINUOUS SUBCUTANEOUS ADMINISTRATION OF INTERFERON-ALPHA TO HEPATITIS C INFECTED PATIENTS

• US 20110027229A1
• Filed: 08/02/2010
• Published: 02/03/2011
• Est. Priority Date: 07/31/2009
• Status: Abandoned Application

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: De Knegt, Robert J., Van Antwerp, William P., Grovender, Eric A., Janssen, Harry L. A.
• Application Number:
  US12/848,856
• Publication Number:
  US 20110027229A1
• Time in Patent Office: Days
• US Class Current: 424/85.7
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61P 31/14 for RNA viruses

Abstract

Methods and systems for treating Hepatitis C infections are provided. Typically the method comprises administering interferon-α to the patient subcutaneously using a continuous infusion apparatus, wherein this therapeutic regimen is sufficient to maintain circulating levels of interferon-α in the serum of the patient above a target concentration for a certain period of time.

Claims

1. A method of administering interferon-α

to a patient infected with hepatitis C virus, the method comprising;

administering interferon-α

to the patient using a continuous infusion apparatus, wherein the interferon-α

is administered to the patient using a therapeutic regimen sufficient to maintain circulating levels of the interferon-α

in the serum of the patient above a mean steady state concentration of 100 pg/mL for at least 1 week to at least 48 weeks.

2. The method of claim 1, wherein the therapeutic regimen is sufficient to maintain circulating levels of the interferon-α

in the patient above a mean steady state concentration of at least 200, 300, 400, 500, 600 or 700 pg/mL.

3. The method of claim 1, wherein the method further comprises determining a polynucleotide sequence of the patient, wherein the polynucleotide sequence comprises a single nucleotide polymorphism (SNP) designated rs12979860, rs12980275, rs8099917, rs12972991, rs8109886, rs4803223, rs8103142, rs28416813, rs4803219, rs4803217, rs581930, rs8105790, rs11881222, rs7248668 or rs12980602.

4. The method of claim 3, wherein the SNP is rs12979860 and the method comprises determining if the patient comprises a CC genotype, a TT genotype or a CT genotype.

5. The method of claim 3, further comprising using polynucleotide sequence information to determine or modulate a parameter of the therapeutic regimen, wherein the parameter comprises:

a duration of interferon-α

administration;

or

an interferon-α

dose.

6. The method of claim 1, further comprising identifying the patient as a relapser or a non-responder.

7. The method of claim 1, further comprising identifying the hepatitis C virus as being a genotype 1 or a genotype 4 virus.

8. The method of claim 1, wherein the therapeutic regimen is administered for a duration of at least 5, 6, 7, 8, 12, 24, 36 or 48 weeks.

9. The method of claim 1, wherein the therapeutic regimen is sufficient to reduce levels of HCV in the patient by at least 2 logs (100-fold) or 3 logs (1000 fold) after 1, 2, 4, 8 10, 12, 14 or 16 weeks.

10. The method of claim 1, wherein the interferon-α

is not conjugated to a polyol.

11. A method of administering an interferon-α

to a patient infected with hepatitis C virus, the method comprising;

(a) administering a dose of interferon-α

to the patient;

(b) observing a concentration of circulating interferon-α

in serum of the patient that results from the dose of interferon-α

;

(c) using the concentration of circulating interferon-α

observed in step (b) to make a patient-specific therapeutic regimen, wherein the patient specific therapeutic regimen comprises administering interferon-α

to the patient subcutaneously using a continuous infusion apparatus in an amount sufficient to maintain circulating levels of interferon-α

in the serum of the patient above a steady state concentration of at least 100 pg/mL.

12. The method of claim 11, wherein the method further comprises:

determining a polynucleotide sequence of the patient, wherein the polynucleotide sequence comprises a single nucleotide polymorphism (SNP) designated rs12979860, rs12980275, rs8099917, rs12972991, rs8109886, rs4803223, rs8103142, rs28416813, rs4803219, rs4803217, rs581930, rs8105790, rs11881222, rs7248668 or rs12980602; and

using polynucleotide sequence information to determine or modulate a parameter of the patient-specific therapeutic regimen, wherein the parameter comprises;

a duration of interferon-α

administration;

or

an interferon-α

dose.

13. The method of claim 11, further comprising:

identifying the patient as a relapser or a non-responder;

identifying the hepatitis C virus as being a genotype 1 or a genotype 4 virus;

observing in vitro proliferation of T cells from the patient in response to exposure to interferon-α

;

administering interferon-α

that is not conjugated to a polyol;

or

administered interferon-α

to the patient using a patient-specific therapeutic regimen sufficient to maintain circulating levels of interferon-α

in the serum of the patient above a steady state concentration of at least 200, 300, 400, 500, 600 or 700 pg/mL for at least 1 week to at least 48 weeks.

14. The method of claim 11, wherein:

the patient-specific therapeutic regimen is administered for a duration of at least 5, 6, 7, 8, 12, 24, 36 or 48 weeks;

or

the patient-specific therapeutic regimen is sufficient to reduce levels of HCV in the patient by at least 2 logs (100-fold) or 3 logs (1000 fold) after 1, 2, 4, 8 10, 12, 14 or 16 weeks.

15. A system for administering interferon-α

to a patient having a hepatitis C infection, the system comprising;

a continuous infusion pump having a medication reservoir comprising interferon-α

;

a processor operably connected to the continuous infusion pump and comprising a set of instructions that causes the continuous infusion pump to administer the interferon-α

to the patient according to a therapeutic regimen comprising administering interferon-α

to the patient subcutaneously;

wherein the therapeutic regimen is sufficient to maintain circulating levels of interferon-α

in the serum of the patient above a steady state concentration of at least 100 pg/mL for at least 1 week to at least 48 weeks.

16. The system of claim 15, wherein:

(a) the hepatitis C virus is a genotype 1 HCV;

(b) the hepatitis C virus is a genotype 4 HCV;

(c) the patient is identified as a relapser prior to administering the interferon-α

;

(d) the patient is identified as a non-responder prior to administering the interferon-α

;

(e) the therapeutic regimen is sufficient to maintain circulating levels of interferon-α

in the patient above a concentration of at least 200, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675 or 700 pg/mL;

(f) the therapeutic regimen is administered for a duration of at least 4, 8, 12, 24, 36 or 48 weeks;

(g) the therapeutic regimen is sufficient to reduce levels of HCV in the patient by at least 2 logs (100-fold) or 3 logs (1000 fold) after 1, 2, 4, 8 10, 12, 14 or 16 weeks;

or

(h) the interferon-α

is not conjugated to a polyol.

17. The system of claim 15, wherein:

a polynucleotide sequence of the patient using the system is determined, the polynucleotide sequence comprising a single nucleotide polymorphism (SNP) designated rs12979860, rs12980275, rs8099917, rs12972991, rs8109886, rs4803223, rs8103142, rs28416813, rs4803219, rs4803217, rs581930, rs8105790, rs11881222, rs7248668 or rs12980602; and

the processor in the system is used to modulate a parameter of the patient-specific therapeutic regimen using determined polynucleotide sequence information, wherein the parameter comprises;

a duration of interferon-α

administration;

or

an interferon-α

dose.

18. The system for administering interferon-α

of claim 15, wherein the system for administering interferon-α

is coupled to an electronic system for managing medical data on an electronic communication network, the electronic system comprising;

at least one electronic server connectable for communication on the communication network, the at least one electronic server being configured for;

receiving information on a first physiological parameter observed in a patient;

setting a first dosage of the interferon-α

for infusion by the continuous infusion pump, based on the first physiological parameter;

receiving second physiological parameter information of the patient indicative of a response of the patient to the interferon-α

of the first dosage; and

setting a second dosage of the interferon-α

for infusion by the continuous infusion pump, based on the second physiological parameter.

19. The system of claim 15, wherein the continuous infusion pump:

has dimensions smaller than 15×

15 centimeters;

or

is operably coupled to an interface that facilitates the patient'"'"'s movements while using the continuous infusion pump, wherein the interface comprises a clip, a strap, a snap, a clamp or an adhesive strip.

20. Use of interferon-α

in the manufacture of a composition for treating hepatitis C infection for use in a continuous infusion apparatus, wherein the interferon-α

composition is manufactured to allow the continuous infusion apparatus to maintain mean circulating levels of interferon-α

in serum of a patient above a steady state concentration of at least 100 pg/mL for at least 1 to at least 48 weeks when administered subcutaneously.