WO2012175700A1 - Traitement de l'hépatite c chronique avec ifn-a5 en combinaison avec ifn-a2b dans une cohorte de patients - Google Patents

Traitement de l'hépatite c chronique avec ifn-a5 en combinaison avec ifn-a2b dans une cohorte de patients Download PDF

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WO2012175700A1
WO2012175700A1 PCT/EP2012/062128 EP2012062128W WO2012175700A1 WO 2012175700 A1 WO2012175700 A1 WO 2012175700A1 EP 2012062128 W EP2012062128 W EP 2012062128W WO 2012175700 A1 WO2012175700 A1 WO 2012175700A1
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Prior art keywords
ifn
patients
hcv
treatment
genotype
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PCT/EP2012/062128
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English (en)
Inventor
Francisco Javier CÁMARA MARTÍN
Iranzu GONZÁLEZ DE LA TAJADA
Pablo Miguel ORTIZ BETÉS
Juan RUIZ ECHEVERRÍA
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Digna Biotech, S. L.
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Priority to BR112013032188A priority Critical patent/BR112013032188A2/pt
Priority to CN201280030232.0A priority patent/CN103732242A/zh
Priority to RU2014102102/15A priority patent/RU2014102102A/ru
Publication of WO2012175700A1 publication Critical patent/WO2012175700A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A61K38/212—IFN-alpha
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the field of the invention is in pharmacology and medical treatments, particularly in clinical uses or methods of treatment of Hepatitis C virus (HCV) infected patients.
  • HCV Hepatitis C virus
  • HCV Hepatitis C virus
  • HCV Hepatitis C virus
  • spherical, enveloped, positive-strand R A viruses [1-2].
  • HCV has emerged as a major viral pandemic over the past two decades, with about 3% of the world's population chronically infected [3].
  • Chronic HCV infection is defined as persistent, detectable serum HCV RNA for a period greater than 6 months, with or without derangement in liver function tests. This is in contrast to acute HCV infection, in which serum HCV RNA clears within 6 months.
  • Prospective studies have shown that 60-85% of HCV-infected people will develop chronic infection [2].
  • genotype 1 is the predominant genotype (70%) in US and Europe and the most resistant to treatment [4], followed by genotypes 2 and 3 (10 and 20%>) [5-7].
  • Treatment with pegylated Alpha interferon (PeglFNa) injections (once a week subcutaneously) combined with oral ribavirin (RBV) over 24 to 48 weeks represent the standard of care (SOC) and induce sustained virologic response (SVR, undetectable HCV RNA at 6 months following treatment discontinuation) in up to 80% of genotype-2 and -3 infected patients, but in only 50% of genotype- 1 infected patients [8-11].
  • This treatment regimen is associated with a multitude of side effects including depression-related effects, neutropenia, thrombocytopenia, injection- site reactions, arthralgia, headache, fatigue, myalgia, insomnia, and nausea.
  • re-treatment with PEG- IFN plus ribavirin can increase the frequency of responsiveness to approximately 20%; for nonresponders to a previous course of standard IFN plus ribavirin, re-treatment with PEG-IFN plus ribavirin can increase the frequency of responsiveness to approximately 10%.
  • Expectations for responsiveness to re-treatment are lower in patients with genotype 1 , cirrhosis, high baseline HCV RNA levels, and black ethnicity.
  • Evidence-based practice aims to provide health care guided by a thoughtful integration of the best available scientific knowledge with clinical expertise. This approach allows the practitioner to critically assess research data, clinical guidelines, and other information resources in order to correctly identify the clinical problem, apply the most high-quality intervention, and re-evaluate the outcome for future improvement. In this respect, the results provided by randomised controlled trials as a means of reliably informing healthcare practice is fundamental.
  • the inventors designed and performed randomized controlled trials with IFN-a5, IFN-a2b, alone or in combination.
  • Type I interferons are a family of polypeptides with cytokine activity which were originally discovered by virtue of their inhibitory activity on the viral infection of cells lines in vitro
  • Human type I interferons include a multigene family of different IFN- subtypes and a single IFN- ?. All type I IFNs are structurally related and share the same IFN receptor.
  • IFN-a5 is the major subtype expressed in PBMC from healthy controls and hepatitis C patients.
  • Patent EP 1077068 discloses uses of interferon alpha 5 in the treatment of viral hepatopathies, particularly chronic hepatitis C. The same patent disclosure submits on paragraph [0044] that no correlation was found between the expression of the IFNa or IFN ? genes in the liver or PBMC and C virus RNA levels in serum or the viral genotype.
  • Yanai et al. J Interferon Cytokine Res. 2001 21(10), 835-41) disclose the antiviral effect of different IFN subtypes and subtype combinations on different cell lines cultures infected with vesicular stomatitis virus.
  • the prior art teachings relate to in vitro experiments that are non-conclusive studies performed on laboratory material eventually derived from unidentified patient sub-groups. Therefore, the tests described in the prior art do not allow any prediction to be made as to whether or not a treatment according to the present invention would bring about any therapeutic improvement in terms of viral response to SOC treatment-experienced patients.
  • an object of the present invention is the provision of an evidence-based therapy for treating chronic hepatitis C in a defined patient cohort, thereby avoiding treating other patients for whom the therapy is not beneficial.
  • One of the technical teachings of the present invention demonstrates that patients where HCV- R A detection occurs after SOC therapy is discontinued, or alternatively after IFN-a2 therapy is stopped, that is during the 6 months post-standard of care (post-SOC) treatment period, i.e.
  • relapsing to a previous SOC treatment benefit most from a treatment with IFN-a5 in combination with IFN-a2b, as shown by an improved antiviral response, i.e., by a reduction of the viral load of the patients' serum in at least 0.5 log, or in at least around 1 log, respectively following 29 days of treatment, in comparison to the antiviral response of the same patient cohort treated with IFN-a5 or IFN-a2b, alone.
  • An additional technical teaching of the present invention demonstrates that relapsers who are infected with the hepatitis C genotype type 1 virus benefit most from a treatment with IFN-a5, in combination with IFN-a2b, as shown by an improved antiviral response, i.e., the diminishing of the viral load of the patients' serum in at least 0.5 log, or in at least around 1 log, respectively, following treatment discontinuation after 29 days) in comparison to the antiviral response of the same patient cohort treated with IFN-a5 or IFN-a2b, alone.
  • a further interesting technical teaching of the present invention demonstrates the synergic and beneficial effect of the combination of IFN-a5 with IFN-a2b in the above described cohort of patients, i.e. relapsers in general, and those relapsers infected with the hepatitis C genotype type 1 virus.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN- a2.
  • the patients are treatment-experienced patients.
  • IFN-alpha2 is selected from IFN-alpha2a (IFN-a2a) and IFN-alpha2b
  • the present invention also relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, in an optimal proportion of 50 % IFN-a5 / 50 % IFN-a2b (w/w) or from a range of 10 % IFN-a5 / 90% IFN-a2b to 90% IFN-a5 / 10% IFN-a2b.
  • the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the HCV genotype 1 is selected from la, lb, and mixed la/lb.
  • the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT.
  • the treatment-experienced patients are selected from non- responders, partial responders, relapsers, and breakthroughs.
  • the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-alpha2 (IFN-a2), for use as an anti-hepatitis C virus (HCV) drug in patients with chronic hepatitis C.
  • IFN-a2 IFN-alpha2
  • HCV anti-hepatitis C virus
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN- a2.
  • Interferon alpha-5 abbreviated as IFN-alpha-5, IFN-a5, Hu-IFN-aG, Hu-IFN-a5, and a.k.a.
  • Interferon alpha-61, Interferon alpha-G, or LeIF G is a human protein naturally produced by macrophages and belongs to the alpha/beta interferon family. It has the following sequence of 189 amino acids long (SEQ ID NO. 1):
  • Human interferon alpha-5 is disclosed for example in Uniprot database (www.uniprot.org) with Accession Number P01569.
  • Amino acids 1 to 21 correspond to the signal peptide.
  • Amino acids 22 to 189 correspond to the secreted protein (168 amino acids length, underlined sequence).
  • "Interferon alpha-2”, abbreviated as IFN-alpha-2, IFN-alpha2 , IFN-a2 and LeIF A is also a human protein naturally produced by macrophages and belongs to the alpha/beta interferon family.
  • Human interferon alpha-2 is disclosed for example in Uniprot with Accession Number P01563.
  • Complete human interferon alpha-2 is a 188 amino acids length protein: amino acids 1 to 23 correspond to the signal peptide.
  • Amino acids 24 to 188 correspond to the secreted protein (165 amino acids length).
  • Interferon alpha-2 Several natural variations of Interferon alpha-2 have been disclosed as polymorphisms: Interferon alpha-2a, alpha-2b and alpha-2c.
  • Interferon alpha-2 as used here in refers to any of these natural variations or recombinantly produced proteins with the same amino acid sequences than these natural variations.
  • Interferon alpha-2a abbreviated as IFN-alpha-2a, IFN-a2a, has the sequence represented by SEQ ID NO. 4:
  • Interferon alpha-2b abbreviated as IFN-alpha-2b, IFN-a2b, has the sequence represented by SEQ ID NO. 5:
  • Interferon alpha-2a is commercially available from Roche with the tradename Roferon-A®.
  • Interferon alpha-2b is commercially available from Schering Corporation with the tradename Intron A®, and formulations and preparations thereof are described in US5, 935,566 and
  • Typical suitable IFN-a5, IFN-a2a and IFN-a2b for the present invention include, but are not limited to human IFN-a5, IFN-a2a, or IFN-a2b, respectively, of natural origin or recombinant human IFN-a5, IFN-a2a, or IFN-a2b, available for example from R&D Systems.
  • the present invention also includes bioequivalent forms and formulations of IFN-a5, IFN-a2a and IFN-a2b, also named biosimilars, as approved by the FDA (United States Food and Drug Administration), EMEA (European Medicines Agency), and other regulatory bodies.
  • Combinations of IFN-a5 and IFN-a2a in the present invention are preferably in an optimal proportion of 50 % IFN-a5 / 50 % IFN-a2a (w/w), or alternatively from a range of 10 % IFN-a5 / 90% IFN-a2a to 90% IFN-a5 / 10% IFN-a2a.
  • Combinations of IFN-a5 and IFN-a2b in the present invention are preferably in an optimal proportion of 50 % IFN-a5 / 50 % IFN-a2b (w/w), or alternatively from a range of 10 % IFN-a5 / 90% IFN-a2b to 90% IFN-a5 / 10% IFN-a2b.
  • Bio equivalence is defined by the FDA as the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or
  • IFN-a5, IFN-a2a, and IFN-a2b proteins may be obtained from a variety of cell sources that synthesize bioactive IFN-a5, IFN-a2a, or IFN-a2b proteins, respectively, including, for example, cells that naturally produce this protein, or cells transfected with recombinant DNA molecules capable of directing the synthesis or secretion of the protein.
  • IFN-a5, IFN-a2a, and IFN-a2b proteins may be synthesized by chemical synthetic methods, including but not limited to, solid phase peptide synthesis.
  • recombinant protein refers to the protein as obtained by DNA recombinant techniques from prokaryotic or eukaryotic host cells as well as its salts, functional derivatives, variants, analogs, and fragments.
  • recombinant IFN-a5, IFN-a2a, or IFN-a2b may be obtained from genetically engineered Escherichia coli bacterium comprising DNA that codes for the human protein, followed by fermentation in a suitable nutrient medium.
  • salts herein refers to both salts of carboxyl groups and to acid addition salts of amino groups of the IFN-a5, IFN-a2a, and IFN-a2b molecule or analogs thereof.
  • Salts of a carboxyl group may be formed by means known in the art and include inorganic salts, for example, sodium, calcium, ammonium, ferric, or zinc salts, and the like, and salts with organic bases as those formed, for example, with amines, such as triethanolamine, arginine, lysine, piperidine, procaine, and the like.
  • Acid addition salts include, for example, salts with mineral acids, such as, for example, hydrochloric acid or sulfuric acid, and salts with organic acids, such as, for example, acetic acid or oxalic acid.
  • mineral acids such as, for example, hydrochloric acid or sulfuric acid
  • organic acids such as, for example, acetic acid or oxalic acid.
  • any such salt must retain the biological activity of IFN-a5, IFN-a2a, or IFN-a2b.
  • salts of IFN-a5, IFN-a2a, or IFN-a2b are those wherein the counter-ion is pharmaceutically acceptable.
  • Non-pharmaceutically acceptable salts are also encompassed in the ambit of the present invention since they can be used in the production of pharmaceutically acceptable end products.
  • “Functional derivatives” as used herein covers derivatives which may be prepared from the functional groups which occur as side chains on the residues or the N- or C-terminal groups, by means known in the art, and are included in the invention as long as they remain
  • compositions containing it may have chemical moieties, such as carbohydrate or phosphate residues, provided such a derivative retains the biological activity of the protein and remains pharmaceutically acceptable.
  • derivatives may include aliphatic esters of the carboxyl groups, amides of the carboxyl groups by reaction with ammonia or with primary or secondary amines, N-acyl derivatives or free amino groups of the amino acid residues formed with acyl moieties (e.g., alkanoyl or carbocyclic aroyl groups), or O-acyl derivatives of free hydroxyl group (e.g., that of seryl or threonyl residues) formed with acyl moieties.
  • Such derivatives may also include for example, polyethylene glycol side-chains, which may mask antigenic sites and extend the residence of the molecule in body fluids.
  • IFN-a5 IFN-a2a
  • IFN-a2b IFN-a2b protein
  • pegylated versions or those genetically engineered to exhibit long lasting activity in the body, can be used according to the present invention.
  • variant refers to a molecule, which is substantially similar to either the entire protein defined above or a fragment thereof. Variant proteins or peptides may be conveniently prepared by direct chemical synthesis of the variant molecule, using methods well known in the art. Of course, such variant would have similar receptor binding and signal initiating activity as the corresponding naturally occurring protein.
  • variants in the protein primary structure are within the scope of the invention.
  • the protein molecules may include conservative or non-conservative alterations in the amino acid sequence that result in silent changes that preserve the functionality of the molecule including, for example, deletions, additions, and substitutions. Such altered molecules may be desirable where they provide certain advantages in their use.
  • conservative substitutions would involve the substitution of one or more amino acids within the sequence of the corresponding protein with another amino acid having similar polarity and
  • Such conservative substitutions include but are not limited to substitutions within the following groups of amino acids: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid; asparagine, glutamine; serine, threonine; lysine, arginine; phenylalanine, tyrosine; and
  • Amino acid sequence variants of the IFN-a5, IFN-a2a, or IFN-a2b protein can be prepared by mutations in the DNAs, which encode the synthesized derivatives. Such variants include, for example, deletions from, or insertions or substitutions of, residues within the amino acid sequence. Any combination of deletion, insertion, and substitution may also be made to arrive at the final construct, provided that the final construct possesses the desired activity. Obviously, the mutations that will be made in the DNA encoding the variant protein must not alter the reading frame and preferably will not create complementary regions that could produce secondary mR A structure.
  • these variants ordinarily are prepared by site-directed mutagenesis of nucleotides in the DNA encoding the protein molecule, thereby producing DNA encoding the variant, and thereafter expressing the DNA in recombinant cell culture.
  • the variants typically exhibit the same qualitative biological activity as the non- variant protein.
  • an "analog" of the IFN-a5, IFN-a2a, or IFN-a2b protein according to the present invention refers to a non-natural molecule, which is substantially similar to either, the entire molecule or to an active fragment thereof.
  • the similarity can be calculated in sequence similarity and is at least 70%, preferably at least 75%, 80%, 85%, 90%, or 95%.
  • Such analog would exhibit the same activity as the corresponding naturally occurring protein.
  • a “fragment” according to the present invention refers to any subset of the IFN-a5, IFN-a2a, or IFN-a2b protein molecule, that is, a shorter peptide, which retains the desired biological activity. Fragments may readily be prepared by removing amino acids from either end of the molecule and testing the resultant for its properties as a receptor agonist. Proteases for removing one amino acid at a time from either the N-terminal or the C-terminal of a polypeptide are known in the art.
  • treatment-experienced patient refers to a patient having an HCV infection with viremia (HCV R A measured by PCR) who has initiated some form of anti-HCV therapy, including but not limited to interferon-alpha, pegylated interferon alpha or ribavirin.
  • treatment-na ' ive patient refers to a patient having an HCV infection with viremia (HCV RNA measured by PCR) and who have not been previously treated with ribavirin or any interferon-based regimen including, but not limited to an interferon-alpha.
  • Treatment-experienced patients may be selected from non-responders, partial responders, relapsers, and breakthroughs.
  • non-responder patient refers to a patient having a HCV infection with viremia (HCV RNA measured by PCR) and who has previously been treated and fails to achieve sustained virologic response.
  • HCV infection with viremia HCV RNA measured by PCR
  • sustained virologic response refers to undetectable HCV RNA levels for 6 months after completion of therapy.
  • partial responder refers to a patient having a HCV infection with viremia (HCV R A measured by PCR) and who has previously been treated and fails to achieve 2 log drop versus baseline viral load despite at least twelve weeks of PEG-Intron (pegylated interferon) 1.5 mcg/kg/week plus weight based RBV (ribavirin) (>10.6 mg/kg/day).
  • the application of this definition accommodates a 0.5 log variation of the definition, however, so that if an individual patient achieves as high as a 2.5 log drop versus baseline, or anywhere between 2 and 2.5 log drop versus baseline viral load despite at least twelve weeks of PEG-Intron (pegylated interferon) 1.5 mcg/kg/week plus weight based RBV (ribavirin) (>10.6 mg/kg/day), it would be within the discretion of the investigator to denominate the patient as a "non-responder" on a case by case basis.
  • PEG-Intron pegylated interferon
  • RBV ribavirin
  • a responder is defined as a patient who completed the treatment phase of the study and reported SVR, i.e. for at least 6 months.
  • relapse refers to that patient, in which there is a return of a sign, symptom, or disease after a remission. More particularly, relapsers are those CHC patients who had achieved virologic response (HCV-RNA non-detectable) at any time during the standard care of treatment for CHC with IFN-a2 or PegIFN-a2 + ribavirin, and maintained it through the end of treatment at week 48 weeks, but HCV-RNA detection occurs before 6 months post-treatment.
  • chronic when relating to diseases, refers to diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by
  • CHC Chronic Hepatitis C.
  • chronic hepatitis C (CHC) infection is meant those patients diagnosed by seropositivity for anti-HCV antibodies or detectable HCV-RNA, in an interval of at least 6 months.
  • the diagnosis of chronic hepatitis C is based on the detection of HCV infection (positive anti-HCV antibodies and HCV RNA) in a patient with signs of chronic hepatitis.
  • a patient suffering from chronic hepatitis C infection may additionally exhibit, and without being limited to, one or more of the following signs or symptoms: elevated ALT, clinical stigmata of chronic liver disease, hepatocellular damage.
  • the term "no detectable HCV RNA” or “undetectable HCV RNA” in the present invention means that there is 50 IU/ml or less of HCV RNA levels in a patient serum as measured by quantitative, multi-cycle reverse transcriptase PCR methodology, ideally by a real-time PCR assay such as Abbott RealTimeTM HCV and the like.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in patients with chronic hepatitis C.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in patients with chronic hepatitis C.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN- a2 wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to a method of treating treatment- experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to a method of treating treatment- experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to a method of treating treatment- experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN- a2a, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN- a2b, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2 wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb.
  • genotype 1 la, lb or mixed la/lb
  • Patients with CHC infection of genotype 1 may be confirmed by genotype testing at screening.
  • genotypes la and lb of HCV are both well known to one skilled in the art.
  • Holland, J. et al "Hepatitis C Genotyping by Dire.O
  • patients treated may also carry HCV of genotype 2, 3, 4, 5, 6, or any mixed genotype (1/2, 1/3, 1/4, 2/3, 3/4, 3/6), diagnosed by genotypic testing at screening; may also have Hepatitis B virus (HBV) infection based on the presence of HBsAg; may also have Hepatitis A virus (HAV) infection based on the presence of antiHAV-IgM; or may also be positive ELISA for HIV-1 or HIV-2. Also patients may present quasispecies variants of HCV.
  • HCV Hepatitis B virus
  • HAV Hepatitis A virus
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients have a genotype of the single nucleotide
  • polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method
  • IFN-a5 and IFN-a2a comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the treatments of the present invention are useful for treating patients for whom treatment for one or more symptoms associated with HCV genotype 1 (la, lb or mixed la/lb) is indicated, or patients for whom previous interferon therapy, meaning other than the composition comprising IFN-a5 and IFN-a2, has proved ineffective.
  • ineffective in the context of patients having had previous interferon therapy, meaning other than the composition comprising IFN-a5 and IFN-a2, which proved to be ineffective, the definition of "ineffective” is failure to achieve at least about a 2 log drop versus baseline viral load despite at least twelve weeks of therapy including interferon alone or in combination with other active agents in which the interferon is administered at about 1.5 mcg/kg/week.
  • This definition of "ineffective” further embraces that if the interferon(s) (i.e.
  • the combination active agent may be ribavirin, or a wide variety of other agents, as well as either the presence or absence of viral rebound after the treatment period deemed to be "ineffective.”
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype selected 1 selected from la, lb, and mixed la/lb, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the
  • IFN-a5 and IFN-a2 wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the
  • IFN-a5 and IFN-a2a wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the
  • IFN-a5 and IFN-a2b administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the
  • IFN-a5 and IFN-a2 administration of a therapeutically effective amount of IFN-a5 and IFN-a2, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2a, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the
  • IFN-a5 and IFN-a2a administration of a therapeutically effective amount of IFN-a5 and IFN-a2a, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to the composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the
  • IFN-a5 and IFN-a2b administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN- a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the IFN-a5 is
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with HCV genotype 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with HCV genotype 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-hepatitis C virus (HCV) drug patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • HCV hepatitis C virus
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-hepatitis C virus (HCV) drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • HCV hepatitis C virus
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the
  • IFN-a5 and IFN-a2b administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN- a2b, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the treatment-experienced patients are selected from non- responders, partial responders, relapsers, and breakthroughs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients have a genotype of the single nucleotide polymorphism
  • rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the treatment-experienced patients are selected from non- responders, partial responders, relapsers, and breakthroughs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating treatment- experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN-a2b, for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide
  • polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a method of treating treatment-experienced patients with chronic hepatitis C, said method comprising the administration of a therapeutically effective amount of IFN-a5 and IFN-a2b, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the treatment-experienced patients are selected from non- responders, partial responders, relapsers, and breakthroughs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C.
  • any formulation comprising the product or composition of the invention, may additionally comprises excipients, adjuvants, and any other convenient pharmaceutical ingredients, including other drugs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C. In one embodiment, the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb.
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, and wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential
  • HCV 1 use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, and wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/ lb, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, and wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • Anti-HCV drugs encompass compounds selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV polymerase inhibitors include, but are not limited to, NM283 (valopicitabine), R803, JTK- 109, JTK-003, HCV-371, HCV-086, HCV-796 and R-1479.
  • Inhibitors of HCV proteases include, but are not limited to, the compounds of WO02/18369 (see, e.g., page 273, lines 9-22 and page 274, line 4 to page 276, line 11); BILN-2061, VX-950, GS-9132 (ACH-806), SCH-503034, and SCH-6. Further agents that can be used are those disclosed in W098/17679, WO00/056331 (Vertex); WO 98/22496 (Roche); WO 99/07734, (Boehringer Ingelheim), WO 2005/073216, WO
  • Inhibitors of other targets in the HCV life cycle including NS3 helicase; metallo-protease inhibitors; antisense oligonucleotide inhibitors, such as ISIS- 14803, AVI-4065 and the like;
  • siRNA's such as SIRPLEX-140-N and the like; vector-encoded short hairpin RNA (shRNA); DNAzymes; HCV specific ribozymes such as heptazyme, RPI.13919 and the like; entry inhibitors such as HepeX-C, HuMax-HepC and the like; alpha glucosidase inhibitors such as celgosivir, UT-231B and the like; KPE-02003002; and BIVN 401.
  • shRNA vector-encoded short hairpin RNA
  • DNAzymes HCV specific ribozymes such as heptazyme, RPI.13919 and the like
  • entry inhibitors such as HepeX-C, HuMax-HepC and the like
  • alpha glucosidase inhibitors such as celgosivir, UT-231B and the like
  • KPE-02003002 KPE-02003002
  • BIVN 401 BIVN 401.
  • Immunomodulatory agents include, but are not limited to; natural and recombinant interferon isoform compounds, including IFN-a, IFN- ⁇ , IFN- ⁇ , IFN- ⁇ and the like, such as Roferon-A® (recombinant interferon alpha-2a), Canferon-A300®, Advaferon®, Infergen®, Humoferon®, Sumiferon MP®, Alfaferone®, IFN-beta®, Feron®, Berofor® (recombinant interferon alpha- 2C), interferon alpha-nl, a purified blend of natural alpha interferons such as Sumiferon available from Sumitomo or as Wellferon interferon alpha-nl (INS) available from Glaxo-Wellcome; or a consensus interferon alpha such as those described in Patent Nos.
  • natural and recombinant interferon isoform compounds including IFN-a, IFN- ⁇ , IFN- ⁇ , IFN
  • interferon alpha-n3 which is a mixture of natural interferon alphas.
  • interferon include polyethylene glycol derivatized (pegylated) interferon compounds, such as PEG interferon-a-2a (Pegasys®), PEG interferon-a-2b (PEG-Intron®), pegylated IFN-a-conl and the like; long acting formulations and derivatizations of interferon compounds such as the albumin-fused interferon albuferon a and the like.
  • interferons of the beta type include Avonex® or Rebif ® (interferon-beta-la), Betaseron® (interferon-beta-lb).
  • the IFN-beta-la in Avonex® is the glycosylated, native human sequence whereas the IFN-beta-lb in Betaseron® is the unglycosylated, serine 17-substituted, native human sequence.
  • immunomodulatory agents include compounds that stimulate the synthesis of interferon in cells, such as resiquimod and the like; interleukins; compounds that enhance the development of type 1 helper T cell response, such as SCV-07 and the like; TOLL-like receptor agonists such as CpG- 10101 (actilon), isatoribine and the like; thymosin a-1; ANA-245; ANA-246; histamine dihydrochloride; propagermanium; tetrachlorodecaoxide; ampligen; IMP-321; KRN-7000;
  • antibodies such as civacir, XTL-6865 and the like; and prophylactic and therapeutic vaccines such as InnoVac C, HCV E1E2/MF59 and the like.
  • antiviral agents include, but are not limited to, ribavirin, amantadine, viramidine, nitazoxanide; telbivudine; NOV-205; taribavirin; inhibitors of internal ribosome entry; broad- spectrum viral inhibitors, such as IMPDH inhibitors (e.g., compounds of U.S. Pat. No. 5,807,876, U.S. Pat. No. 6,498,178, U.S. Pat. No. 6,344,465, U.S. Pat. No.
  • IMPDH inhibitors e.g., compounds of U.S. Pat. No. 5,807,876, U.S. Pat. No. 6,498,178, U.S. Pat. No. 6,344,465, U.S. Pat. No.
  • cardiotrophin refers to the cytokine cardiotrophin-1, a.k.a. CT-1, as well as to cardiotrophin-like cytokines.
  • oncostatin M refers to the cytokine a.k.a. OSM, as well as to OSM-like cytokines.
  • OSM was originally isolated from medium conditioned by PMA-treated U-937 human histiocytic leukemia cells based on its ability to inhibit growth of A375 melanoma cells.
  • the human OSM cDNA encodes a 252 amino acid pre-pro-OSM polypeptide with a 25 residue hydrophobic signal peptide and a hydrophilic C-terminal domain that are proteolytically processed to generate the 196 residue mature form of OSM.
  • accession number for this protein can be found in the publicly available protein database at http://www.expasy.org/uniprot/P13725.
  • the amino acid sequence of human OSM is the following represented by SEQ ID NO. 2:
  • the cytokines CT-1 or OSM relate to the complete native form of said cytokine; or any active fraction of said cytokine, that is, any partial polypeptide sequence of said cytokine which maintains the physiological effects of the complete cytokine claimed in the present invention; and any polypeptide derivative of said cytokine, that is, any polypeptide sequence which has a sequence identity greater than 70% with said native cytokine and maintains the physiological effects of the complete cytokine claimed in the present invention.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, further comprising a third anti- HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, further comprising a third anti- HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, further comprising a third anti- HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 and the HCV genotype 1 is selected from la, lb, and mixed la/lb, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN- a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN- a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN- a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN- a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN- a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN- a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb supplement wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-hepatitis C virus (HCV) drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype 1 selected from la, lb, and mixed la/lb, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HC V protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HC V protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN- a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN- a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the treatment- experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 selected from la, lb, and mixed la/lb, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN- a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 selected from la, lb, and mixed la/lb, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients are infected with HCV genotype 1 selected from la, lb, and mixed la/lb, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the treatment-experienced patients are selected from non- responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immuno
  • the present invention relates to a product containing IFN-a5 and IFN- a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the treatment-experienced patients are selected from non- responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the treatment-experienced patients are selected from non- responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN- a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the patients are infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixes thereof, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • the present invention relates to a product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rs 12979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the patients are infected with HCV genotype 1 selected from la, lb, and mixed la/lb, wherein the treatment-experienced patients are selected from non- responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an H
  • the present invention relates to a product containing IFN-a5 and IFN- a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the patients are infected with HCV genotype 1 selected from la, lb, and mixed la/lb, wherein the treatment-experienced patients are selected from non- responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected
  • the present invention relates to a product containing IFN-a5 and IFN- a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT, wherein the patients are infected with HCV genotype 1 selected from la, lb, and mixed la/lb, wherein the treatment-experienced patients are selected from non- responders, partial responders, relapsers, and breakthroughs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected
  • inventions of the present invention are those mentioned above in respect to the product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, further comprising a third anti-HCV drug selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, or a recombinant version thereof.
  • a third anti-HCV drug selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, or a recombinant version thereof.
  • inventions of the present invention are those mentioned above in respect to the product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, further comprising a third anti-HCV drug selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, or a recombinant version thereof.
  • a third anti-HCV drug selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, or a recombinant version thereof.
  • inventions of the present invention are those mentioned above in respect to the product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in patients with chronic hepatitis C, further comprising a third anti-HCV drug selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, or a recombinant version thereof.
  • a third anti-HCV drug selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, or a recombinant version thereof.
  • FIG. 1 Further embodiments of the present invention, are those mentioned above in respect to the product containing IFN-a5 and IFN-a2 as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, further comprising a third anti-HCV drug selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, or a recombinant version thereof.
  • a third anti-HCV drug selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, or a recombinant version thereof.
  • inventions of the present invention are those mentioned above in respect to the product containing IFN-a5 and IFN-a2a as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, further comprising a third anti-HCV drug selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, or a recombinant version thereof.
  • a third anti-HCV drug selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, or a recombinant version thereof.
  • FIG. 1 Further embodiments of the present invention, are those mentioned above in respect to the product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, further comprising a third anti-HCV drug selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, or a recombinant version thereof.
  • a third anti-HCV drug selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, or a recombinant version thereof.
  • Preferred embodiments of the present invention are those mentioned above in respect to the product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the interferon alpha- 2b is administered at a dosage of about 1.5 MIU, TIW.
  • the present invention relates to a composition comprising IFN-a5 and IFN- a2b, for use in the treatment of patients infected with HCV, characterized in that the HCV is genotype 1.
  • the present invention relates to a composition comprising IFN-a5 and IFN- a2b, for use in the treatment of patients infected with HCV, characterized in that patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • a further embodiment of the present invention relates to a composition comprising IFN-a5 and IFN-a2baccording to any one of the two preceding paragraphs, wherein the HCV infection is chronic.
  • a further embodiment of the present invention relates to a composition comprising IFN-a5 and IFN-a2b according to any one of the three preceding paragraphs, wherein the patients are treatment-experienced patients.
  • a further embodiment of the present invention relates to a composition comprising IFN-a5 and IFN-a2b according to the preceding paragraph, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • a further embodiment of the present invention relates to a composition comprising IFN-a5 and IFN-a2b according to any one of thefive preceding paragraphs, wherein the HCV genotype 1 is selected from la, lb, and mixed la/lb.
  • a further embodiment of the present invention relates to a composition comprising IFN-a5 and IFN-a2b according to any one of the six preceding paragraphs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the IFN-a2b is administered at a dosage of about 1.5 MIU, TIW).
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, in the treatment of patients infected with hepatitis C virus (HCV), characterized in that the HCV is genotype 1.
  • HCV hepatitis C virus
  • the present invention relates to a product containing IFN-a5 and IFN-a2b as a combined preparation for simultaneous, separate, or sequential use, in the treatment of patients infected with hepatitis C virus (HCV), characterized in that patients have a genotype of the single nucleotide polymorphism rsl2979860 on chromosome 19ql3 selected from CC, CT, and TT, preferably CT or TT.
  • HCV hepatitis C virus
  • a further embodiment of the present invention relates to the product according to any one of the two preceding paragraphs, wherein the HCV infection is chronic.
  • a further embodiment of the present invention relates to the product according to any one of the three preceding paragraphs, wherein the patients are treatment-experienced patients.
  • a further embodiment of the present invention relates to the product according to the preceding paragraph, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers, and breakthroughs.
  • a further embodiment of the present invention relates to the product according to any one of the five preceding paragraphs, wherein the HCV genotype 1 is selected from la, lb, and mixed la/lb.
  • a further embodiment of the present invention relates to the product according to any one of the six preceding paragraphs, further comprising a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a third anti-HCV drug selected from an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, cardiotrophin, oncostatin M, and combinations thereof.
  • a further embodiment of the present invention relates to the product according to the preceding paragraph, wherein the third anti-HCV drug is selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, a consensus interferon, a purified interferon alpha product, and a recombinant version thereof .
  • a further embodiment of the present invention relates to the product according to any one of the eight preceding paragraphs, wherein the IFN-a5 is administered at a dosage of about 1.5 MIU, TIW, and the interferon alpha-2b is administered at a dosage of about 1.5 MIU, TIW.
  • IFN-a5 with either IFN-a2a or IFN-a2b, preferably IFN-a2b, and optionally a third anti-HCV drug as mentioned above are administered to the patient, as defined in any one of the embodiments above, in a sufficiently effective amount.
  • IFN-a5, IFN-a2a, and IFN-a2b may be formulated into various pharmaceutical forms for administration purposes.
  • compositions there may be cited all compositions usually employed for systemically administering drugs.
  • effective amounts of IFN-a5, either IFN-a2a or IFN-a2b, preferably IFN-a2b, and optionally a third anti-HCV drug as mentioned above, as the active ingredients are combined in intimate admixture with a pharmaceutically acceptable carrier, which carrier may take a wide variety of forms depending on the manner of preparation desired for administration.
  • compositions are desirable in unitary dosage form suitable, particularly, for administration orally, rectally, transdermally, by inhalation, or by parenteral routes (i.e., subcutaneous, intravenous, intramuscular, or intraperitoneal).
  • IFN-a5 either IFN-a2a or IFN-a2b, and optionally a third anti-HCV drug, can be administered by the oral route in solid dosage forms, such as tablets, capsules, and powders, or in liquid dosage forms, such as elixirs, syrups, and suspensions.
  • the pharmaceutical compositions of this invention can also be administered parenterally, in sterile liquid dosage forms.
  • administration are those parenteral routes, particularly by intramuscular, intravenous, or subcutaneous injections.
  • Formulations for parenteral administration may be in the form of aqueous or non-aqueous isotonic sterile injection solutions or suspensions.
  • Injectable solutions for example, may be prepared, in which the carrier comprises saline solution, glucose solution or a mixture of saline and glucose solution.
  • Injectable suspensions may also be prepared in which case appropriate liquid carriers, suspending agents and the like may be employed.
  • solid form preparations that are intended to be converted, shortly before use, to liquid form preparations.
  • the carrier optionally comprises a penetration-enhancing agent and/or a suitable wetting agent, optionally combined with suitable additives of any nature in minor proportions, which additives do not introduce a significant deleterious effect on the skin.
  • suitable additives may be anti-oxidants, preservatives, stabilizing agents, emulsifiers, salts for influencing the osmotic pressure, and/or buffer
  • IFN-a5 either IFN-a2a or IFN-a2b, preferably IFN-a2b, and optionally a third anti-HCV drug, may be may be delivered to the epithelial cells formulated in liposomes.
  • Liposomes can be prepared using conventional techniques including sonication, chelate dialysis, homogenization, solvent infusion coupled with extrusion, freeze-thaw extrusion,
  • Reagents used to crosslink a liposome or other lipid- containing agent to the proteins of the present invention comprise a phospholipid derivative to anchor one end of the crosslink in the lipid layer and a reactive group at the other end to provide a point of attachment to the target biomolecule.
  • Polymerized liposomes or liposomes coated with polymer may as well be used. Such polymers may stabilize the liposome, reduce its clearance from the body, and/or reduce its immunogenicity.
  • the liposome may be loaded with a functional moiety such as a diagnostic or therapeutic agent either during or after its formation.
  • the agent may be contained in an aqueous core of the liposome or can be incorporated into or attached to its surrounding membrane.
  • Unit dosage form refers to physically discrete units suitable as unitary dosages, each unit containing a predetermined quantity of active ingredient calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier.
  • unit dosage forms are tablets (including scored or coated tablets), capsules, pills, suppositories, powder packets, wafers, injectable solutions or suspensions and the like, and segregated multiples thereof.
  • the daily dosage of the compounds according to the invention shall vary with the mode of administration, the treatment desired, and the severity of the disorder.
  • an effective amount of IFN-a5 would be from 1 to 10 MIU daily or three times a week, preferably from 1 to 5 MIU daily or three times a week, more preferably at a dosage of 3 MIU three times a week.
  • IFNa2a is usually administered at 11. ⁇ g/0.5mL, 22 ⁇ g/0.5mL, 33.3 ⁇ g/0.5mL, daily or three times a week.
  • IFNa2b is usually administered at 0.038mg/lmL, 0.069mg/lmL, 0.087mg/1.5mL, 0.144mg/1.5mL, 0.192mg/lmL, 0.288mg/1.5mL, by injection three or five times a week.
  • IFNpia is usually administered at 8 ⁇ g/0.5mL, 22 ⁇ g/0.5mL, or 44 ⁇ g/0.5mL injected
  • IFNpib is usually administered at 0.0625mg / 0.25mL and increased to 0.25mg/lmL injected subcutaneously every other day.
  • the recommended dosage of INTRON-A interferon alpha 2b (commercially available from Schering-Plough Corp.) as administered by subcutaneous injection at 3MIU(12 mcg)/0.5 mL/TIW is for 24 weeks or 48 weeks for first time treatment.
  • the recommended dosage of PEG- INTRON interferon alpha 2b pegylated (commercially available from Schering-Plough Corp.) as administered by subcutaneous injection at 1.5 mcg/kg/week, within a range of 40 to 150 meg/week, is for at least 24 weeks.
  • ROFERON A interferon alpha 2a (commercially available from Hoffmann-La Roche) as administered by subcutaneous or intramuscular injection at 3MIU(11.1 mcg/mL)/TIW is for at least 48 to 52 weeks, or
  • the recommended dosage of PEGASUS interferon alpha 2a pegylated (commercially available from Hoffmann-La Roche) as administered by subcutaneous injection at 180 mcg/1 mL or 180 mcg/0.5 mL is once a week for at least 24 weeks.
  • the recommended dosage of INFERGEN interferon alphacon-1 (commercially available from Amgen) as administered by subcutaneous injection at 9 mcg/TIW is for 24 weeks for first time treatment and up to 15 mcg/TIW for 24 weeks for non-responsive or relapse treatment.
  • ribavirin a synthetic nucleoside analogue with activity against a broad spectrum of viruses including HCV
  • the recommended dosage of ribavirin is in a range from 600 to 1400 mg per day for at least 24 weeks (commercially available as Rebetol ribavirin from Schering-Plough or Copegus ribavirin from Hoffmann-La Roche).
  • IFN-a5 + IFN-a2b for 29 days in combined therapy at the same total dose of 3 MIU divided into equal doses of 1.5 MIU of IFN-a5 and 1.5 MIU of IFN-a2b, administered subcutaneously of each agent, 3 times a week;
  • IFN-a2b for 29 days in monotherapy at doses of 3 MIU administered subcutaneously, 3 times a week. IFN-a2b has proven efficacy in achieving SVR in CHC infected patients against placebo.
  • CHC chronic hepatitis C
  • genotype 1 (la, lb or mixed la/ lb) confirmed by genotype testing at screening.
  • relapsers those CHC patients who had achieved viral response (HCV-RNA non- detectable) at any time during the standard care of treatment for CHC with IFN-a2 or PegIFN-a2 + ribavirin, and maintained it through the end of treatment at week 48 weeks, but HCV-RNA detection occured before 6 months post-treatment.
  • liver cirrhosis had been ruled out through fibro-scan or liver biopsy within 24
  • ALT alaninaminotransferase
  • AST aspartate-aminotransferase
  • BMI body mass index
  • HBV Hepatitis B virus
  • Descompensated liver disease or history of decompensated liver disease, as evidenced by ascites, portal hypertension, jaundice or hepatic encephalopathy, coagulopathy, varices, history of variceal bleeding or any other clinical evidence of decompensation.
  • Alfa-fetoprotein value >100ng/mL at screening. If >20ng/mL and ⁇ 100 ng/mL, patients could be included if there was no evidence of liver cancer in two congruent imaging studies (e.g. ultrasound, CT scan, MRI) within 6 months past from first visit.
  • congruent imaging studies e.g. ultrasound, CT scan, MRI
  • Haemoglobinopathy e.g. thalassemia major or sickle cell anaemia.
  • Any chronic viral (including HSV), bacterial, mycobacterial, fungal, parasitic, or protozoal infection including HSV, bacterial, mycobacterial, fungal, parasitic, or protozoal infection.
  • the administered Interferon-a5 was a recombinant human protein IFN-a5, 167 amino acids long, and with the sequence (SEQ ID NO 3): MCDLPQTHSLSNRRTLMIMAQMGRISPFSCLKDRHDFGFPQEEFDGNQFQKAQAISVLH
  • Interferon-a2b Interferon-a2b (IntronA®), as solution for subcutaneous injection, was provided by study sponsor, Digna Biotech (Spain), and was obtained from Shering Plough (USA), in Multidose Pens for Injection 1.5 mL.
  • One pen of Strength 3 MIU contained 6 doses, 0.2 mL each. 3 MIU in 0.2 mL.
  • Eligible patients were randomised to one of the three treatment arms at Visit -1.
  • the CRO was the provider of the randomization used in this trial. Patients were randomly assigned between the three available arms, depending on study phase.
  • Table 1 Per Protocol, patients, per treatment group.
  • Treatment Arm patient number, result of nucleotide sequence (CC, CT or TT) near the gene encoding IL28B, HCV Log scale viral load on day 1 -before treatment- and day 29 of treatment, and viral load decrease per patient.
  • Treatment Arm patient number, result of nucleotide sequence (CT or TT) near the gene encoding IL28B, HCV Log scale viral load on day 1 -before treatment- and day 29 of treatment, and viral load decrease per patient
  • Treatment Arm patient number, result of nucleotide sequence (CT or TT) near the gene encoding IL28B, HCV Log scale viral load on day 1 -before treatment- and day 29 of treatment, and viral load decrease per patient.
  • CT or TT nucleotide sequence
  • treatment B i.e. the combination of IFN-a5 + IFN-a2b
  • treatment B showed the best results in the rate of patients reaching more than 0.5 Log HCV viral load decrease in treatment at day 29, and also in the total decrease of viral load at day 29 of treatment, in patients with a CT or TT nucleotide sequence in the polymorphism located in chromosome 19, close to the region coding for IL28B.
  • Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004 Mar 2;140(5):346-55. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiftman M, Reindollar R, et al. Peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep

Abstract

La présente invention concerne l'interféron alpha 5 (IFN-a5) en combinaison avec l'interféron alpha 2 (IFN-a2), destiné à être utilisé en tant qu'un médicament contre le virus de l'hépatite C (VHC) chez des patients souffrant d'hépatite C chronique. Plus particulièrement, la présente invention concerne un procédé de traitement de patients souffrant d'hépatite C chronique, ledit procédé comprenant l'administration d'une quantité thérapeutiquement efficace d'IFN-a5 en combinaison avec l'IFN-a2. Selon un mode de réalisation, la présente invention concerne un produit contenant l'IFN-a5 et l'IFN-a2 sous la forme d'une préparation combinée pour une utilisation simultanée, séparée, ou séquentielle, en tant que médicament contre l'hépatite C chez des patients souffrant d'hépatite C chronique.
PCT/EP2012/062128 2011-06-23 2012-06-22 Traitement de l'hépatite c chronique avec ifn-a5 en combinaison avec ifn-a2b dans une cohorte de patients WO2012175700A1 (fr)

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BR112013032188A BR112013032188A2 (pt) 2011-06-23 2012-06-22 composição, produto e método para tratar pacientes com hepatite c crônica
CN201280030232.0A CN103732242A (zh) 2011-06-23 2012-06-22 用与IFN-α2b组合的IFN-α5在患者群体中治疗慢性丙型肝炎
RU2014102102/15A RU2014102102A (ru) 2011-06-23 2012-06-22 КОМПОЗИЦИЯ И КОМБИНИРОВАННЫЙ ПРЕПАРАТ ИНТЕРФЕРОНА-а5 С ИНТЕРФЕРОНОМ-а2 И СПОСОБ ЛЕЧЕНИЯ ХРОНИЧЕСКОГО ГЕПАТИТА С

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