CN103732242A - Treatment of chronic hepatitis C in a patient population with IFN-α5 in combination with IFN-α2b - Google Patents

Abstract

The present invention relates to interferon alpha 5 (IFN-α5) in combination with interferon alpha 2 (IFN-α2) for use as an anti-hepatitis C virus (HCV) drug in patients suffering from chronic hepatitis C. Or in other words, the present invention relates to a method for treating patients suffering from chronic hepatitis C, the method comprising administering a therapeutically effective amount of IFN-α5 in combination with IFN-α2. In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients suffering from chronic hepatitis C.

Description

Treatment of chronic hepatitis C in a patient population with IFN-α5 in combination with IFN-α2b

technical field

The invention belongs to the field of pharmacology and medical treatment, in particular to the clinical application or method of treating patients infected with hepatitis C virus (Hepatitis C virus, HCV).

Background technique

Hepatitis C virus (HCV), identified in 1989, is a member of the flaviviridae family and is a spherical, enveloped, positive-sense RNA virus [1-2]. HCV has emerged as a major viral pandemic over the past two decades, with approximately 3% of the world's population chronically infected [3]. Chronic HCV infection was defined as persistent, detectable serum HCV RNA over a period of greater than 6 months, with or without disturbances in liver function tests. In contrast, serum HCV RNA cleared within 6 months in acute HCV infection. Prospective studies have shown that 60 to 85% of HCV-infected patients will develop chronic infection [2].

There are six different HCV genotypes that are prevalent in different geographic regions, with genotype 1 being the dominant genotype (70%) in the United States and Europe and the most resistant to treatment [4], followed by genotype 2 and 3 (10% and 20%) [5-7].

Existing HCV antiviral drugs are associated with limited efficacy and significant toxicity. Combination treatment with pegylated interferon alfa (PegIFNα) injections (once weekly subcutaneously) and oral ribavirin (RBV) for 24 to 48 weeks represents standard of care (SOC) and is effective in up to Sustained virologic response (SVR, undetectable HCV RNA 6 months after treatment cessation) was induced in 80% of patients infected with genotypes 2 and 3, but only in 50% of patients infected with genotype 1 A sustained virological response is induced in patients [8-11]. This regimen is associated with a variety of side effects, including depression-related effects, neutropenia, thrombocytopenia, injection site reactions, arthralgia, headache, fatigue, myalgia, insomnia, and nausea .

With each advance in antiviral therapy for chronic hepatitis C (CHC), patients who have failed to clear the virus or have relapsed after existing therapy are treated again, in the hope that newer treatments will be available in patients treated for the first time As established in , the better efficacy of newer treatments will extend to them as well. Therefore, patients who relapsed or failed to respond to 6 months of interferon (IFN) monotherapy were treated with higher doses of IFN or for a longer duration [12,13], and subsequently with a combination of IFN and RBV[ 14-17] The treatment is performed again. The latter study established a sustained virologic response (SVR) rate of 50% in current IFN relapsers [16,17] and, in meta-analyses, in current IFN nonresponders Sustained virologic response rates of 13% to 15% [18, 19]. Although PegIFN-α+RBV has shown good efficacy in treatment-naive patients, among relapsers, only 32% to 55% of patients achieved SVR, and genotype 1 patients had A low SVR rate [20, 21] leaves at least another 50% at risk of serious and life-threatening progression of the underlying disease. Furthermore, a recent trial showed that longer courses of low-dose PegIFNα did not reduce the rate of disease progression in patients with CHC and advanced fibrosis (with or without cirrhosis) who had previously been unresponsive to SOC therapy [22].

Retreatment with PEG-IFN plus ribavirin increased the frequency of response to approximately 20% in nonresponders to a prior standard course of IFN monotherapy; For responders, retreatment with PEG-IFN plus ribavirin increased the frequency of response to approximately 10%. Expectations of response to retreatment were lower in patients with genotype 1, cirrhosis, high baseline HCV RNA levels, and being black.

Given the poor SVR rates to existing therapies in treatment-naïve patients infected with HCV genotype 1, and also in HCV-infected relapsers and nonresponders to existing therapies, it needs to be used in these specific patient populations more effective and less toxic treatments.

The purpose of evidence-based practice is to provide health care guided by the thoughtful integration of the best available scientific knowledge and clinical experience. This approach allows practitioners to critically evaluate research data, clinical guidelines, and other sources of information to correctly identify clinical problems, apply interventions of the highest quality, and reevaluate outcomes for future improvements. For this reason, the results provided by randomized controlled trials are fundamental as a way to reliably inform healthcare practice.

In order to provide a treatment supported by evidence-based medicine, the inventors designed and carried out a randomized controlled trial with IFN-α5, IFN-α2b alone or in combination.

Type I interferons are a family of polypeptides with cytokine activity that were first discovered by virtue of their inhibitory activity on viral infection of cell lines in vitro (Pestka et al., 2004). Human type I interferons comprise a multigene family of different IFN-α subtypes and a single IFN-β. All type I IFNs are structurally related and share the same IFN receptor.

Castel Ruiz et al. (Hepatology 1999; 29: 1900-1904) teach that IFN-α5 is the subtype mainly expressed in liver tissue and that IFN-α is decreased in the liver of patients with chronic HCV infection. By this statement, the authors speculate that IFN-α5 may play a role in the treatment of chronic hepatitis C (see last column on page 1903, last paragraph of Discussion).

Larrea et al. (J Viral Hepat. 2001; 8: 103-110) disclosed that IFN-α5 is a subtype mainly expressed in PBMCs of healthy controls and hepatitis C patients.

Patent EP1077068 (Instituto Científico y Tecnológico de Navarra) discloses the use of interferon alpha 5 in the treatment of viral liver diseases, especially chronic hepatitis C. The patent disclosure states at paragraph [0044] that no correlation was found between IFNα or IFNβ gene expression in liver or PBMC and serum C virus RNA levels or viral genotype.

Yanai et al. (J Interferon Cytokine Res. 2001 21(10), 835-41) disclosed the antiviral effects of different IFN subtypes and combinations of subtypes on cultures of different cell lines infected with herpetic stomatitis virus.

To the best of the inventors' knowledge, the prior art has not involved clinical studies involving tissues: IFN-α5, IFN-α2b, or both at 50% IFN-α5/50% IFN-α2b (w/w) or 10% The optimal ratio combination of IFN-α5/90% IFN-α2b to 90% IFN-α5/10% IFN-α2b, not to mention the treatment of HCV infection in patients with chronic hepatitis C, let alone experienced Treatment of HCV infection in patients with chronic hepatitis C. Variously, all experiments disclosed in the prior art were performed using infected laboratory cell lines or biopsy material from HCV-infected patients. The prior art teachings relate to in vitro experiments performed as inconclusive studies using laboratory material ultimately derived from unidentified subgroups of patients. Therefore, the tests described in the prior art do not allow to make any predictions as to whether the treatment according to the invention will bring about any therapeutic improvement in the viral response of patients who have undergone SOC treatment.

It is therefore an object of the present invention to provide an evidence-based therapy for the treatment of chronic hepatitis C in a particular patient population, thereby avoiding the treatment of other patients for whom the therapy would not benefit.

One of the technical teachings of the present invention shows that patients with HCV-RNA detection (i.e. in previous SOCs who relapsed after treatment ("relapsers")) benefited most from treatment with IFN-α5 in combination with IFN-α2b, as indicated by an improved antiviral response, i.e., after 29 days of treatment, compared with treatment with IFN-α2b alone The viral load in patient serum is reduced by at least 0.5 log, or at least about 1 log, compared to the antiviral response of the same patient population treated with IFN-α5 or IFN-α2b, respectively.

Another technical teaching of the present invention shows that relapsers infected with hepatitis C genotype 1 virus benefit most from treatment with IFN-α5 in combination with IFN-α2b, as indicated by an increased antiviral response, i.e. , after 29 days of cessation of treatment, the viral load in the patient's serum is reduced by at least 0.5 log, or at least about 1 log, compared to the antiviral response of the same patient population treated with IFN-α5 or IFN-α2b alone, respectively.

Another interesting technical teaching of the present invention shows the synergy of the combination of IFN-α5 and IFN-α2b in the above patient populations (i.e. general relapsers, and those relapsers infected with hepatitis C genotype 1 virus) and beneficial effects.

Summary of the invention

The present invention relates to a method of treating a patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2.

In one embodiment of the invention, said patient is a therapy experienced patient. In another embodiment, the IFN-α2 is selected from IFN-α2a and IFN-α2b.

The present invention also relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising: 50% IFN-α5/50% IFN-α2b (w/w) or 10% IFN-α5/90 Optimal ratio of % IFN-α2b to 90% IFN-α5/10% IFN-α2b Therapeutically effective amounts of IFN-α5 and IFN-α2b are administered.

In one embodiment of the invention, said patient is infected with an HCV genotype selected from the group consisting of 1, 2, 3, 4, 5, 6 and mixtures thereof.

In one embodiment of the invention, said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b.

In one embodiment of the present invention, the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT.

In one embodiment of the invention, said treatment-experienced patients are selected from non-responders, partial responders, relapsers and rebounders.

In one embodiment of the invention, IFN-α5 is administered at a dose of about 1.5 MIU, TIW and IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

Detailed description of the invention

The present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-hepatitis C virus (HCV) drug in patients with chronic hepatitis C. Or in other words, the present invention relates to a method of treating a patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2.

Interferon α5 is abbreviated as IFN-α-5, IFN-α5, Hu-IFN-αG, Hu-IFN-α5, and is also known as Interferon α-61, Interferon α-G or LeIF G, which is produced by giant Human protein produced naturally by phagocytes and belongs to the alpha/beta interferon family. It has the following sequence (SEQ ID NO.1) of 189 amino acids in length:

MALPFVLLMALVVLNCKSICS LGCDLPQTHSLSNNRRTLMIMAQMGRISPF

SCLKDRHDFG FPQEEFDGNQ FQKAQAISVL HEMIQQTFNL FSTKDSSATW

DETLLDKFYT ELYQQLNDLE ACMMQEVGVE DTPLMNVDSI LTVRKYFQRI

TLYLTEKKYS PCAWEVVRAE IMRSFSLSAN LQERLRRKE .

Human interferon alpha-5 is disclosed, for example, in the Uniprot database (www.uniprot.org) under 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 in length, underlined sequence).

"Interferon alpha-2", abbreviated as IFN-alpha-2, IFN-alpha2, IFN-alpha2, 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 eg in Uniprot under accession number P01563. Intact human interferon alpha-2 is a protein of 188 amino acids in length: amino acids 1 to 23 correspond to the signal peptide. Amino acids 24 to 188 correspond to the secreted protein (165 amino acids in length).

Several natural variations of interferon alpha-2 have been disclosed as polymorphisms: interferon alpha-2a, alpha-2b and alpha-2c. As used herein, interferon alpha-2 refers to any of these natural variants or a recombinantly produced protein with the same amino acid sequence as these natural variants.

Interferon α-2a is abbreviated as IFN-α-2a, IFN-α2a, which has the sequence shown in SEQ ID NO.4:

MALTFALLVALLVLSCKSSCSVGCDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDF

GFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLE

ACVIQGVGVTFTPLMKFDSILAVRKYFQRITLYLKFKKYSPCAWFVVRAFIMRSFSLSTN

LQFSLRSKE .

Underlined sequences correspond to secreted proteins.

Interferon α-2b is abbreviated as IFN-α-2b, IFN-α2b, which has the sequence shown in SEQ ID NO.5:

MALTFALLVALLVLSCKSSCSVG CDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFG

FPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEA

CVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNL

QESLRSKE .

Underlined sequences correspond to secreted proteins.

市购自Roche。Interferon alfa-2a under the trademark

Commercially available from Roche.

Interferon alfa-2b under the trademark Commercially available from Schering Corporation and its formulation and preparation are described in US 5,935,566 and US 6,610,830.

Typical suitable IFN-α5, IFN-α2a and IFN-α2b for use in the present invention include, but are not limited to: human IFN-α5, IFN-α2a or IFN-α2b of natural origin, or recombinant human IFN-α5, IFN-α2b, respectively. - α2a or IFN-α2b, available for example from R&D Systems. The present invention also includes bioequivalent forms and formulations of IFN-α5, IFN-α2a and IFN-α2b (also referred to as as biosimilars).

The combination of IFN-α5 and IFN-α2a in the present invention is preferably the following optimal ratio: 50% IFN-α5/50% IFN-α2a (w/w) or 10% IFN-α5/90% IFN-α2a to 90 %IFN-α5/10%IFN-α2a.

The combination of JFN-α5 and IFN-α2b in the present invention is preferably the following optimal ratio: 50% IFN-α5/50% IFN-α2b (w/w) or 10% IFN-α5/90% IFN-α2b to 90% IFN-α5/10% IFN-α2b.

Bioequivalence is defined by the FDA as: The active ingredient or active moiety of a drug equivalent or drug substitute that becomes available at the drug's site of action when administered at the same molar dose under similar conditions in appropriately designed studies There were no significant differences in rate and extent.

IFN-α5, IFN-α2a, and IFN-α2b proteins can be obtained from a variety of cellular sources that synthesize biologically active IFN-α5, IFN-α2a, or IFN-α2b protein, respectively, including, for example, cells that naturally produce the proteins or transfected A cell having a recombinant DNA molecule capable of directing the synthesis or secretion of said protein. Alternatively, IFN-α5, IFN-α2a and IFN-α2b proteins can be synthesized by chemical synthesis methods, including but not limited to solid phase peptide synthesis.

The term "recombinant protein" used in the present invention in relation to IFN-α5, IFN-α2a or IFN-α2b refers to proteins and their salts, functional derivatives, variants such as obtained from prokaryotic or eukaryotic host cells by DNA recombinant technology , analogs and fragments. In general, recombinant IFN-α5, IFN-α2a or IFN-α2b can be obtained by genetically engineering Escherichia coli containing DNA encoding human protein, followed by fermentation in a suitable nutrient medium.

The term "salt" herein refers to both salts of carboxyl groups and acid addition salts of amino groups of IFN-α5, IFN-α2a and IFN-α2b molecules or analogs thereof. Salts of carboxyl groups can be formed by methods known in the art, and include inorganic salts, such as sodium, calcium, ammonium, iron, or zinc salts, etc.; and salts with organic bases, for example, with amines (such as triethanolamine), arginine, lysine, piperidine, procaine, etc. Acid addition salts include, for example, salts with mineral acids such as hydrochloric acid or sulfuric acid and salts with organic acids such as acetic acid or oxalic acid. Of course, any such salt must retain the biological activity of IFN-a5, IFN-a2a or IFN-a2b. For therapeutic use, salts of IFN-a5, IFN-a2a or IFN-a2b are those wherein the counterion is pharmaceutically acceptable. Non-pharmaceutically acceptable salts are also encompassed within the scope of this invention, as they may be useful in the production of pharmaceutically acceptable end products.

"Functional derivatives" as used herein encompasses derivatives that can be prepared by methods known in the art from functional groups present in the side chains of residues or from N- or C-terminal groups, and as long as they remain pharmaceutically acceptable, i.e. , they do not destroy the biological activity of the protein as described above, that is, the ability to bind to the corresponding receptor and initiate receptor signal transduction, and do not confer toxicity to the composition comprising said derivative, they are included in the present invention. Derivatives may have chemical moieties, such as carbohydrate or phosphate residues, provided such derivatives retain the biological activity of the protein and remain pharmaceutically acceptable.

For example, derivatives may include aliphatic esters of carboxyl groups, amides of carboxyl groups reacted with ammonia or primary or secondary amines, N-acyl groups of free amino groups of amino acid residues with acyl moieties (e.g., alkanoyl or carbocyclic aroyl). Derivatives, or O-acyl derivatives of a free hydroxyl group (eg, of a seryl or threonyl residue) and an acyl moiety. Such derivatives may also include, for example, polyethylene glycol side chains, which may mask antigenic sites and prolong the residence time of the molecule in body fluids.

Of particular importance are IFN-α5, IFN-α2a or IFN-α2b proteins that are derivatized or combined with complexing agents to become persistent. For example, pegylated forms or those that have been genetically modified to exhibit persistent activity in the body can be used according to the invention.

A "variant" according to the invention refers to a molecule substantially similar to an intact protein or a fragment thereof as defined above. Variant proteins or peptides can be conveniently prepared by direct chemical synthesis of the variant molecule using methods well known in the art. Such variants will, of course, have similar receptor binding and signaling activity as the corresponding native protein.

Alterations of the primary structure of proteins as well as alterations of higher level structural organization (eg, alterations in the type of covalent bonds linking amino acid residues or addition of groups to terminal residues of proteins) are within the scope of the invention. Furthermore, the protein molecule may include conservative or non-conservative changes in amino acid sequence (including, for example, deletions, additions, and substitutions) that result in silent changes that preserve the functionality of the molecule. Such altered molecules may be expected to provide certain advantages in their use. A conservative substitution as used herein would involve replacing one or more amino acids in the sequence of the corresponding protein with another amino acid having similar polarity and hydrophobicity/hydrophilicity characteristics, resulting in a functionally equivalent molecule. Such conservative substitutions include, but are not limited to, substitutions in the following amino acid groups: glycine, alanine, valine, isoleucine, leucine, aspartic acid, glutamic acid, asparagine, glutamine Amide, serine, threonine, lysine, arginine, phenylalanine, tyrosine, and methionine, norleucine.

Amino acid sequence variants of the IFN-α5, IFN-α2a or IFN-α2b proteins can be prepared by making mutations in the DNA encoding the synthetic derivatives. Such variants include, for example, deletions or insertions or substitutions of residues in the amino acid sequence. Any combination of deletions, insertions and substitutions can also be made to arrive at the final construct, provided the final construct possesses the desired activity. Obviously, the mutations to be made in the DNA encoding the variant protein must not alter the reading frame, and preferably will not create complementary regions that would create secondary mRNA structure.

At the genetic level, these variants are conventionally prepared by site-directed mutagenesis of nucleotides in the DNA encoding the protein molecule, resulting in the production of DNA encoding the variant and subsequent expression of the DNA in recombinant cell culture. These variants generally exhibit qualitatively the same biological activity as the non-variant protein.

An "analogue" of the IFN-α5, IFN-α2a or IFN-α2b protein of the present invention refers to a non-natural molecule that is substantially similar to the whole molecule or an active fragment thereof. This similarity can be calculated as sequence similarity and is at least 70%, preferably at least 75%, 80%, 85%, 90% or 95%. Such analogs will exhibit the same activity as the corresponding native protein.

A "fragment" of the present invention refers to any subtype (ie, a shorter peptide) of the IFN-a5, IFN-a2a or IFN-a2b protein molecule that retains the desired biological activity. These fragments can be readily prepared by removing amino acids from both ends of the molecule and testing the resulting properties as receptor agonists. Proteases for removing one amino acid at a time from the N- or C-terminus of a polypeptide are known in the art.

As used herein, the term "treatment-experienced patient" refers to an HCV infection with concomitant viremia (HCV RNA as measured by PCR) and has initiated some form of anti-HCV therapy (including but not limited to interferon alpha, poly pegylated interferon alfa or ribavirin).

The term "treatment-naive patient" refers to a patient with HCV infection with concomitant viremia (HCV RNA measured by PCR) who has not previously been treated with ribavirin or any interferon-based regimen (including but not limited to interferon alfa) treated patients.

Treatment-experienced patients may be selected from: non-responders, partial responders, relapsers, and treatment breakthroughs.

The term "non-responder" as used herein refers to a patient with HCV infection with concomitant viremia (HCV RNA measured by PCR) who was previously treated but failed to achieve a sustained virologic response.

The term "virological breakthrough" or "breakthrough" refers to the reemergence of HCV RNA while the patient is still on treatment.

The term "sustained virologic response" as used herein refers to undetectable HCV RNA levels for 6 months after completion of treatment.

The term "partial responder" refers to patients with HCV infection (HCV RNA as measured by PCR) with concomitant viremia and who were previously treated despite at least 12 weeks of 1.5 microgram/kg/week PEG-INTRON (polyethylene glycol Alcoholated interferon) plus weight-based RBV (ribavirin) (>10.6 mg/kg/day) treatment but still failed to achieve a 2 log reduction in viral load relative to baseline. In practice, however, the application of this definition allows for a 0.5 log change in the definition, so if despite at least 12 weeks of 1.5 μg/kg/week PEG-INTRON (pegylated interferon) plus weight-based RBV ( Bavirin) (>10.6 mg/kg/day), but individual patients achieve up to a 2.5 log reduction from baseline, or any value between 2 log and 2.5 log reduction from baseline viral load, the investigator may Determine whether a patient is a "non-responder" on a case-by-case basis.

In contrast, responders were defined as patients who completed the treatment period of the study and reported SVR (ie, at least 6 months).

The term "relapser" refers to a patient whose signs, symptoms or disease have returned following remission. More specifically, relapsers achieved a virological response (undetectable HCV-RNA) at any time during CHC standard-of-care treatment with IFN-α2 or PegIFN-α2+ribavirin and were treated up to week 48 Those CHC patients who maintained virological response during the termination period, but developed HCV-RNA detection before 6 months after treatment.

The term "chronic" when associated with diseases refers to diseases that have one or more of the following characteristics: they are persistent, leave residual disability, result from irreversible pathological changes, require special training for the patient to recover or can be expected to require prolonged supervision, observation or care. (Health Services Management, 2nd Edition). The acronym CHC refers to chronic hepatitis C.

"Chronic hepatitis C (CHC) infection" means those patients who are diagnosed as being seropositive for anti-HCV antibodies or detectable HCV-RNA at intervals 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 patients with signs of chronic hepatitis.

Patients with chronic hepatitis C infection may also exhibit, but are not 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" of the present invention means as measured by a quantitative multi-cycle reverse transcription PCR method, ideally by a real-time PCR assay (e.g. Abbott RealTime ^™ HCV), etc., The patient has an HCV RNA level of 50 IU/ml or less in the serum.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in patients with chronic hepatitis C. Or in other words, the present invention relates to a method of treating a patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in patients with chronic hepatitis C. Or in other words, the present invention relates to a method of treating a patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from the group consisting of 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes. Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein said patient is infected with a virus selected from 1, 2, 3, 4 , 5, 6 and their mixed HCV genotypes.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and their mixed HCV genotypes.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and their mixed HCV genotypes.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and their mixed HCV genotypes.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from the group consisting of 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes. Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein said patient is infected with a virus selected from 1, 2, 3, 4 , 5, 6 and their mixed HCV genotypes.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes. Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with a virus selected from 1, 2, 3, 4 , 5, 6 and their mixed HCV genotypes.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from the group consisting of 1a, 1b and Mixed 1a/1b HCV genotype 1. Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein said patient is infected with 1a selected from 1a, 1b and mixed HCV genotype 1/1b.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from HCV genotype 1 of 1a, 1b and mixed 1a/1b. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein the patient is infected with a virus selected from the group consisting of 1a, 1b and mixed 1a/1b HCV genotype 1.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from HCV genotype 1 of 1a, 1b and mixed 1a/1b. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein the patient is infected with a virus selected from the group consisting of 1a, 1b and mixed 1a/1b HCV genotype 1.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from HCV genotype 1 of 1a, 1b and mixed 1a/1b. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient is infected with a virus selected from the group consisting of 1a, 1b and mixed 1a/1b HCV genotype 1.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from the group consisting of 1a, 1b and Mixed 1a/1b HCV genotype 1. Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein said patient is infected with 1a selected from 1a, 1b and mixed HCV genotype 1/1b.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from the group consisting of 1a, 1b and Mixed 1a/1b HCV genotype 1. Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with an infection selected from 1a, 1b and mixed 1a HCV genotype 1/1b.

Patients with genotype 1 (1a, 1b or mixed 1a/1b) CHC infection can be confirmed by genotype testing at screening.

Both genotypes 1a and 1b of HCV are well known to those skilled in the art. As a non-limiting example, Holland, J. et al., "Hepatitis C Genotyping by Dire.Oct Sequencing of the Product...," Pathology, Vol. 30, pp. 192-195 (1998), identify HCV in Table 2 The sequences of genotype 1a and genotype 1b have been confirmed known due to the Genbank/EMBL identification provided for each genotype (ie M62321 and D90208 respectively). Other literature provides comparable taxonomic information on HCV genotypes 1a and 1b, including but not limited to Simmonds, KA et al., J. Clin. Microbiol., 31(6), 1493-1503 (1993). Obviously, the patients being treated may also carry genotypes 2, 3, 4, 5, 6 or any combination (1/2, 1/3, 1/4, 2/3, 3/4, 3/6) of HCV; may also have hepatitis B virus (Hepatitis B virus, HBV) infection based on the presence of HBsAg; may also have hepatitis A virus (Hepatitis A virus) based on the presence of anti-HAV-IgM virus, HAV) infection; or positive for HIV-1 or HIV-2 ELISA. Patients may also present quasispecies variants of HCV.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient has a single nucleotide polynucleotide polynucleotide on chromosome 19q13 Morphology rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT). Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein said patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 Have a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient has a single The nucleotide polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT). Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein the patient has a single nucleotide on chromosome 19q13 The polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient has a single The nucleotide polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT). Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein the patient has a single nucleotide on chromosome 19q13 The polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient has a single The nucleotide polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT). Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient has a single nucleotide on chromosome 19q13 The polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient has a single nucleotide polynucleotide polynucleotide on chromosome 19q13 Morphology rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT). Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein said patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 Have a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient has a mononucleotide polynucleotide on chromosome 19q13 Morphology rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT). Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 Have a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from the group consisting of 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT). Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein said patient is infected with a virus selected from 1, 2, 3, 4 , 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, CT and TT (preferably CT or TT) genotype. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, CT and TT (preferably CT or TT) genotype. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, CT and TT (preferably CT or TT) genotype. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from the group consisting of 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT). Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein said patient is infected with a virus selected from 1, 2, 3, 4 , 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT). Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with a virus selected from 1, 2, 3, 4 , 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from the group consisting of 1a, 1b and HCV genotype 1 of mixed 1a/1b, and wherein the patient has a genotype selected from CC, CT and TT (preferably CT or TT) at the single nucleotide polymorphism rs12979860 on chromosome 19q13. Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein said patient is infected with 1a selected from 1a, 1b and mixed HCV genotype 1 of /1b, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from HCV genotype 1 of 1a, 1b and mixed 1a/1b, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT). Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein the patient is infected with a virus selected from the group consisting of 1a, 1b and mixed 1a/1b HCV genotype 1, and wherein the patient has a genotype selected from CC, CT and TT (preferably CT or TT) at the single nucleotide polymorphism rs12979860 on chromosome 19q13.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from HCV genotype 1 of 1a, 1b and mixed 1a/1b, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT). Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein the patient is infected with a virus selected from the group consisting of 1a, 1b and mixed 1a/1b HCV genotype 1, and wherein the patient has a genotype selected from CC, CT and TT (preferably CT or TT) at the single nucleotide polymorphism rs12979860 on chromosome 19q13.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from HCV genotype 1 of 1a, 1b and mixed 1a/1b, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT). Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient is infected with a virus selected from the group consisting of 1a, 1b and mixed 1a/1b HCV genotype 1, and wherein the patient has a genotype selected from CC, CT and TT (preferably CT or TT) at the single nucleotide polymorphism rs12979860 on chromosome 19q13.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from the group consisting of 1a, 1b and HCV genotype 1 of mixed 1a/1b, and wherein the patient has a genotype selected from CC, CT and TT (preferably CT or TT) at the single nucleotide polymorphism rs12979860 on chromosome 19q13. Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein said patient is infected with 1a selected from 1a, 1b and mixed HCV genotype 1 of /1b, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from the group consisting of 1a, 1b and HCV genotype 1 of mixed 1a/1b, and wherein the patient has a genotype selected from CC, CT and TT (preferably CT or TT) at the single nucleotide polymorphism rs12979860 on chromosome 19q13. Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with an infection selected from 1a, 1b and mixed 1a HCV genotype 1 of /1b, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

The methods of treatment of the present invention may be used to treat patients who demonstrate a need for treatment of one or more symptoms associated with HCV genotype 1 (1a, 1b or mixed 1a/1b), or prior interferon therapy (meaning other than those containing Combinations of IFN-α5 and IFN-α2) have been shown to be ineffective for patients.

In the context of "ineffective" in the context of previous interferon therapy (meaning other than a composition comprising IFN-α5 and IFN-α2) that has been shown to be ineffective in the patient, "ineffective" is defined as despite at least 12 weeks of treatment, including interferon alone or in combination with other active agents, where interferon was administered at about 1.5 micrograms/kg/week, failed to achieve at least about a 2 log reduction in viral load from baseline. This definition of "ineffective" also includes if the interferon (i.e., IFN-α5 in combination with IFN-α2) is given in combination therapy, the combination active agent can be ribavirin or a variety of other agents, and the treatment period is considered Subsequent presence or absence of virological rebound was "null".

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said treatment-experienced patient Selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein the treatment-experienced patient is selected from the group consisting of Responders, partial responders, relapsers, and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said treatment-experienced patient Selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein the treatment-experienced patient is selected from the group consisting of Responders, partial responders, relapsers, and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said treatment-experienced patient Selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the treatment-experienced patient is selected from the group consisting of Responders, partial responders, relapsers, and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and mixed HCV genotypes thereof, and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and mixed HCV genotypes thereof, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and mixed HCV genotypes thereof, and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and mixed HCV genotypes thereof, and wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and mixed HCV genotypes thereof, and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and mixed HCV genotypes thereof, and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from HCV genotype 1 of 1a, 1b and mixed 1a/1b, and wherein said treatment experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein the patient is infected with a virus selected from the group consisting of 1a, 1b and mixed 1a/1b HCV genotype 1, and wherein the treatment-experienced patients are selected from the group consisting of non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from HCV genotype 1 of 1a, 1b and mixed 1a/1b, and wherein said treatment experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein the patient is infected with a virus selected from the group consisting of 1a, 1b and mixed 1a/1b HCV genotype 1, and wherein the treatment-experienced patients are selected from the group consisting of non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from HCV genotype 1 of 1a, 1b and mixed 1a/1b, and wherein said treatment experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient is infected with a virus selected from the group consisting of 1a, 1b and mixed 1a/1b HCV genotype 1, and wherein the treatment-experienced patients are selected from the group consisting of non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient has a single Nucleotide polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT), and wherein said treatment-experienced patient is selected from non-responders, partial responders, relapsers and treatment rebounders By. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein the patient has a single nucleotide on chromosome 19q13 The polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT), and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient has a single Nucleotide polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT), and wherein said treatment-experienced patient is selected from non-responders, partial responders, relapsers and treatment rebounders By. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein the patient has a single nucleotide on chromosome 19q13 The polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT), and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient has a single Nucleotide polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT), and wherein said treatment-experienced patient is selected from non-responders, partial responders, relapsers and treatment rebounders By. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient has a single nucleotide on chromosome 19q13 The polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT), and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, CT and TT (preferably CT or TT) genotype, and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and mixed HCV genotypes thereof, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), And wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, CT and TT (preferably CT or TT) genotype, and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and mixed HCV genotypes thereof, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), And wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2, 3, 4, 5, 6 and their mixed HCV genotypes, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, CT and TT (preferably CT or TT) genotype, and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and mixed HCv genotypes thereof, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), And wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2 for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from HCV genotype 1 of 1a, 1b and mixed 1a/1b, and wherein said patient has a genotype selected from the group consisting of CC, CT and TT (preferably CT or TT) at the single nucleotide polymorphism rs12979860 on chromosome 19q13, and Wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2, wherein the patient is infected with a virus selected from the group consisting of 1a, 1b and mixed HCV genotype 1 of 1a/1b, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), and wherein the Treatment-experienced patients were selected from non-responders, partial responders, relapsers, and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2a for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from HCV genotype 1 of 1a, 1b and mixed 1a/1b, and wherein said patient has a genotype selected from the group consisting of CC, CT and TT (preferably CT or TT) at the single nucleotide polymorphism rs12979860 on chromosome 19q13, and Wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2a, wherein the patient is infected with a virus selected from the group consisting of 1a, 1b and mixed HCV genotype 1 of 1a/1b, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), and wherein the Treatment-experienced patients were selected from non-responders, partial responders, relapsers, and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a virus selected from HCV genotype 1 of 1a, 1b and mixed 1a/1b, and wherein said patient has a genotype selected from the group consisting of CC, CT and TT (preferably CT or TT) at the single nucleotide polymorphism rs12979860 on chromosome 19q13, and Wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient is infected with a virus selected from the group consisting of 1a, 1b and mixed HCV genotype 1 of 1a/1b, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), and wherein the Treatment-experienced patients were selected from non-responders, partial responders, relapsers, and treatment rebounders.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in patients with chronic hepatitis C, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW , and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said administration of IFN-α5 The dose is about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with HCV genotype 1, 2, 3, 4, 5, 6, and mixtures thereof, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with HCV genotypes 1, 2, 3, 4, 5, 6, and mixtures thereof, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with HCV Genotypes 1, 2, 3, 4, 5, 6 and mixtures thereof, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with HCV genotype 1, 2, 3, 4, 5, 6, and mixtures thereof, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with HCV genotype 1 and The HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein the IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a patient with chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with HCV genotype 1 and said HCV genotype Type 1 is selected from 1a, 1b and mixed 1a/1b, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with HCV Genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with HCV genotype 1 and The HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein the IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-hepatitis C virus (HCV) drug in a patient with chronic hepatitis C, wherein said patient has chromosomal The single nucleotide polymorphism rs12979860 on 19q13 has a genotype selected from CC, CT and TT (preferably CT or TT), wherein the administration dose of the IFN-α5 is about 1.5 MIU, TIW, and the IFN-α2b The administered dose is about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 Having a genotype selected from CC, CT and TT (preferably CT or TT), wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-hepatitis C virus (HCV) drug in treatment-experienced patients with chronic hepatitis C, wherein The single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), wherein the administration dose of the IFN-α5 is about 1.5MIU, TIW, and the The dose of IFN-α2b administered is about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient has a single nucleotide on chromosome 19q13 Polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT), wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with a virus selected from 1, 2 , 3, 4, 5, 6 and mixed HCV genotypes thereof, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), wherein The IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a patient suffering from chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with a virus selected from 1, 2, 3, 4 , 5, 6 and mixed HCV genotypes thereof, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), wherein the IFN- α5 is administered at a dose of about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a selected HCV genotypes from 1, 2, 3, 4, 5, 6 and their mixture, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, CT and TT (preferably CT or TT) genotype, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and mixed HCV genotypes thereof, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), wherein The IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a patient with chronic hepatitis C, wherein said patient is infected with HCV genotype 1 and The HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT) , wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a patient with chronic hepatitis C, said method comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with HCV genotype 1 and said HCV genotype Type 1 is selected from 1a, 1b and mixed 1a/1b, wherein said patient has a genotype selected from CC, CT and TT (preferably CT or TT) with the single nucleotide polymorphism rs12979860 on chromosome 19q13, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with HCV Genotype 1 and the HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a characteristic selected from CC, CT and TT (preferably CT or TT ), wherein the IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with HCV genotype 1 and The HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT) , wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein the treatment-experienced Patients are selected from non-responders, partial responders, relapsers and treatment rebounders, wherein the IFN-α5 is administered at a dose of about 1.5 MIU, TIW and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW . Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the treatment-experienced patient is selected from the group consisting of Responders, partial responders, relapsers, and treatment rebounders, wherein the IFN-α5 is administered at a dose of about 1.5 MIU, TIW and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is on chromosome 19q13 SNP rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT), wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders or, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient has a single nucleotide on chromosome 19q13 Polymorphism rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT), wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, wherein all The IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a selected HCV genotypes from 1, 2, 3, 4, 5, 6 and mixed thereof, wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, wherein said IFN -α5 is administered at a dose of about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and mixed HCV genotypes thereof, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, wherein the administration of IFN-α5 The dose is about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with a selected HCV genotypes from 1, 2, 3, 4, 5, 6 and their mixture, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, CT and TT (preferably CT or TT) Genotype, wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers, and treatment rebounders, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α5 [alpha]2b was administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein the patient is infected with a virus selected from the group consisting of 1, 2 , 3, 4, 5, 6 and mixed HCV genotypes thereof, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), wherein The treatment-experienced patients are selected from the group consisting of non-responders, partial responders, relapsers and treatment rebounders, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of It is about 1.5MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with HCV Genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, wherein all The IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with HCV genotype 1 and The HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, wherein the IFN-α5 The administered dose of is about 1.5 MIU, TIW, and the administered dose of the IFN-α2b is about 1.5 MIU, TIW.

In another embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use as an anti-HCV drug in a treatment-experienced patient with chronic hepatitis C, wherein said patient is infected with HCV Genotype 1 and the HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a characteristic selected from CC, CT and TT (preferably CT or TT ), wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers, and treatment rebounders, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b was administered at a dose of about 1.5 MIU, TIW. Or in other words, the present invention relates to a method of treating a treatment-experienced patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-α5 and IFN-α2b, wherein said patient is infected with HCV genotype 1 and The HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT) , wherein said treatment-experienced patients are selected from the group consisting of non-responders, partial responders, relapsers, and treatment rebounders, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b The dose administered is about 1.5 MIU, TIW.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C use.

The term "product" is used herein to be equivalent to "composition" when construed under US patent law. Said products or compositions comprising IFN-α5 and IFN-α2 form a functional unity or true combination by purpose-directed application, ie as anti-HCV drug in treatment-experienced patients with chronic hepatitis C. Obviously, any formulation comprising a product or composition of the invention may also comprise excipients, adjuvants and any other convenient pharmaceutical ingredients (including other drugs).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C use.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C use.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C, wherein Said patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and mixtures thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use, wherein said patient is infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6 and mixtures thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein Said patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and mixtures thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use, wherein said patient is infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6 and mixtures thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein Said patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and mixtures thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use, wherein said patient is infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6 and mixtures thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C, wherein Said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein Said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein Said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as anti-HCV drug simultaneously, separately or in treatment-experienced patients with chronic hepatitis C Sequential use wherein said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C, wherein The single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein The single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein The single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C, wherein The patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a gene selected from CC, CT and TT ( A genotype of CT or TT) is preferred.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C For use, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, Genotype of CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein The patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a gene selected from CC, CT and TT ( A genotype of CT or TT) is preferred.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C For use, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, Genotype of CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein The patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a gene selected from CC, CT and TT ( A genotype of CT or TT) is preferred.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C For use, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, Genotype of CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C, wherein The patient is infected with HCV genotype 1 and the HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a gene selected from CC, CT and Genotype of TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, and wherein said patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 selected from Genotypes of CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein The patient is infected with HCV genotype 1 and the HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a gene selected from CC, CT and Genotype of TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, and wherein said patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 selected from Genotypes of CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein The patient is infected with HCV genotype 1 and the HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, and wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a gene selected from CC, CT and Genotype of TT (preferably CT or TT).

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as anti-HCV drug simultaneously, separately or in treatment-experienced patients with chronic hepatitis C Sequential use, wherein the patient is infected with HCV genotype 1 and the HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, and wherein the patient has the selected single nucleotide polymorphism rs12979860 on chromosome 19q13 Genotype from CC, CT and TT (preferably CT or TT).

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use, wherein said treatment-experienced patient is selected from the group consisting of non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use, wherein said treatment-experienced patient is selected from the group consisting of non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use, wherein said treatment-experienced patient is selected from the group consisting of non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein said patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and mixtures thereof, and wherein said treatment-experienced patient is selected from non-responders, partial responders, relapsers and those who rebounded from treatment.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein said patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and mixtures thereof, and wherein said treatment-experienced patient is selected from non-responders, partial responders, relapsers and those who rebounded from treatment.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein said patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and mixtures thereof, and wherein said treatment-experienced patient is selected from non-responders, partial responders, relapsers and those who rebounded from treatment.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, and wherein said treatment-experienced patient is selected from non-responders, partial responders, Relapsers and those who rebounded from treatment.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, and wherein said treatment-experienced patient is selected from non-responders, partial responders, Relapsers and those who rebounded from treatment.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as anti-HCV drug simultaneously, separately or in treatment-experienced patients with chronic hepatitis C Sequential use, wherein the patient is infected with HCV genotype 1 and the HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, and wherein the treatment-experienced patient is selected from non-responders, partial responders , Relapsers and rebounders during treatment.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein said patient has a genotype selected from the group consisting of CC, CT and TT (preferably CT or TT) with the single nucleotide polymorphism rs12979860 on chromosome 19q13, and wherein said treatment-experienced patient is selected from non-responders, Partial responders, relapsers, and treatment rebounders.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein said patient has a genotype selected from the group consisting of CC, CT and TT (preferably CT or TT) with the single nucleotide polymorphism rs12979860 on chromosome 19q13, and wherein said treatment-experienced patient is selected from non-responders, Partial responders, relapsers, and treatment rebounders.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein said patient has a genotype selected from the group consisting of CC, CT and TT (preferably CT or TT) with the single nucleotide polymorphism rs12979860 on chromosome 19q13, and wherein said treatment-experienced patient is selected from non-responders, Partial responders, relapsers, and treatment rebounders.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C For use, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, CT and TT (preferably CT or TT) genotype, and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C For use, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, CT and TT (preferably CT or TT) genotype, and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C For use, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from CC, CT and TT (preferably CT or TT) genotype, and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use, wherein said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein said patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 selected from CC , CT and TT (preferably CT or TT) genotype, and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use, wherein said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein said patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 selected from CC , CT and TT (preferably CT or TT) genotype, and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as anti-HCV drug simultaneously, separately or in treatment-experienced patients with chronic hepatitis C Sequential use, wherein the patient is infected with HCV genotype 1 and the HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, wherein the patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 selected from genotype of CC, CT and TT (preferably CT or TT), and wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C, wherein Said product also comprises a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents , cardiotrophin, oncostatine M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein the product further comprises a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators , antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein Said product also comprises a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents , cardiotrophin, oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCv drugs in treatment-experienced patients with chronic hepatitis C Use wherein the product further comprises a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators , antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein Said product also comprises a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents , cardiotrophin, oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use wherein the product further comprises a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators , antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

Anti-HCV drugs encompass compounds selected from the group consisting of HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, 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.

HCV protease inhibitors (NS2-NS3 inhibitors and NS3-NS4A inhibitors) include, but are not limited to: WO02/18369 (see e.g. page 273, lines 9 to 22 and page 274, lines 4 to 276, Row 11), BILN-2061, VX-950, GS-9132 (ACH-806), SCH-503034, and SCH-6. Other reagents that may be used are those disclosed in WO98/17679, WO00/056331 (Vertex), WO98/22496 (Roche), WO99/07734 (Boehringer Ingelheim), WO2005/073216, WO2005073195 (Medivir) and structurally similar substances.

Inhibitors of other targets in the HCV life cycle include: NS3 helicase; metalloproteinase inhibitors; antisense oligonucleotide inhibitors, such as ISIS-14803, AVI-4065, etc.; siRNA, such as SIRPLEX-140-N, etc.; Vector-encoded short hairpin RNA (shRNA); DNase; HCV-specific ribozyme, such as heptazyme, RPI.13919, etc.; entry inhibitors, such as HepeX-C, HuMax-hepC, etc.; α-glucosidase inhibitors, such as Celgosivir, UT-231B, etc.; KPE-02003002; and BIVN401.

(重组干扰素α-2a)、

(重组干扰素α-2C)、干扰素α-n1、天然α干扰素的纯化共混物，例如可得自Sumitomo的Sumiferon或可得自Glaxo-Wellcome的Wellferon干扰素α-n1(INS)；或复合干扰素(consensus interferon)α，例如专利No.US4897471和US4695623(尤其是其实施例7、8或9)中描述的那些、可得自Amgen的特定产品；或

(干扰素α-n3)，其为天然干扰素α的混合物。干扰素的其他形式包括聚乙二醇衍生化(聚乙二醇化)干扰素化合物，例如PEG干扰素-α-2aPEG干扰素-α-2b聚乙二醇化IFN-α-con1等；持久作用制剂和干扰素化合物的衍生物例如稠合白蛋白的干扰素albuferonα等。β型的其他干扰素包括

或

(干扰素-β-1a)、

(干扰素-β-1b)。

中的IFN-β-1a被糖基化，天然人序列；而

中的IFN-β-1b未被糖基化，丝氨酸17-取代的，天然人序列。免疫调节剂的其他例子包括刺激细胞中合成干扰素的化合物，例如雷西莫特(resiquimod)等；白介素；增强1型辅助T细胞应答之发生的化合物，例如SCV-07等；TOLL-样受体激动剂，例如CpG-10101(actilon)、艾沙托立宾(isatoribine)等；胸腺素α-1；ANA-245；ANA-246；组胺二盐酸盐；丙帕锗(propagermanium)；四氯十氧化物(tetrachlorodecaoxide)；安普利近(ampligen)；IMP-321；KRN-7000；抗体，例如ciVacir、XTL-6865等；以及预防性和治疗性疫苗，例如InnoVac C、HCV E1E2/MF59等。Immunomodulators include, but are not limited to: natural and recombinant interferon isotype compounds, including IFN-alpha, IFN-beta, IFN-gamma, IFN-omega, etc., such as

(recombinant interferon alpha-2a),

(recombinant interferon alpha-2c), interferon alpha-n1, purified blends of native alpha interferon, for example Sumiferon available from Sumitomo or Wellferon interferon alpha-n1 (INS) available from Glaxo-Wellcome; or consensus interferon alpha, such as those described in Patent Nos. US4897471 and US4695623 (especially Examples 7, 8 or 9 thereof), specific products available from Amgen; or

(Interferon alpha-n3), which is a mixture of natural interferon alpha. Other forms of interferon include polyethylene glycol derivatized (pegylated) interferon compounds such as PEG interferon-alpha-2a PEG-IFN-α-2b Pegylated IFN-α-con1, etc.; long-acting preparations and derivatives of interferon compounds such as albumin-fused interferon albuferon α, etc. Other beta interferons include

or

(Interferon-beta-1a),

(Interferon-beta-1b).

IFN-β-1a in is glycosylated, native human sequence; while

IFN-β-1b in unglycosylated, serine 17-substituted, native human sequence. Other examples of immunomodulators include compounds that stimulate the synthesis of interferons in cells, such as resiquimod, etc.; interleukins; compounds that enhance the occurrence of type 1 helper T cell responses, such as SCV-07, etc.; TOLL-like receptors Body agonists, such as CpG-10101 (actilon), isatoribine (isatoribine), etc.; Thymosin α-1; ANA-245; ANA-246; Histamine dihydrochloride; Propagermanium (propagermanium); Tetrachlorodecaoxide; ampligen; IMP-321; KRN-7000; antibodies such as ciVacir, XTL-6865, etc.; and prophylactic and therapeutic vaccines such as InnoVac C, HCV E1E2/ MF59 et al.

Other antiviral agents include but are not limited to ribavirin, amantadine, viramidine, nitazoxanide; telbivudine; NOV-205; taribavirin; Entry inhibitors (inhibitor of internal ribosome entry); broad-spectrum virus inhibitors, such as IMPDH inhibitors (such as US Patent No. 5,807,876, US Patent No. 6,498,178, US Patent No. 6,344,465, US Patent No. /40381, compounds of WO00/56331, and mycophenolic acid and its derivatives, and including but not limited to VX-950, merimepodib (VX-497), VX-148 and/or VX-944); or any combination of the above .

The term "cardiotrophin" refers to the cytokine cardiotrophin-1, also known as CT-1, as well as cardiotrophin-like cytokines.

The term "oncostatin M" refers to cytokines also known as OSM, as well as OSM-like cytokines. OSM was originally isolated from the medium of PMA-treated U-937 human histiocytic leukemia cells conditioned on its ability to inhibit the growth of A375 melanoma cells. 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, which is proteolytically processed to produce 196 residue mature form of OSM. The listed accession numbers 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 shown in SEQ ID NO.2 below:

MGVLLTQRTLLSLVLALLFPSMASMAAIGSCSKEYRVLLGQLQKQTDLMQDTSRLLDPY

IRIQGLDVPKLREHCRERPGAFPSEETLRGLGRRGFLQTLNATLGCVLHRLADLEQRLPK

AQDLERSGLNIEDLEKLQMARPNILGLRNNIYCMAQLLDNSDTAEPTKAGRGASQPPTPT

PASDAFQRKLEGCRFLHGYHRFMHSVGRVFSKWGESPNRSRRHSPHQALRKGVRRTRPS

RKGKRLMTRGQLPR.

The cytokine CT-1 or OSM used in the present invention relates to the intact natural form of said cytokine; or any active fraction of said cytokine, i.e., said cytokine retains the intact cytokine claimed in the present invention Any part of the polypeptide sequence of the physiological role of the cytokine; and any polypeptide derivative of the cytokine, that is, having more than 70% sequence identity with the natural cytokine and retaining the physiological role of the complete cytokine claimed in the present invention any polypeptide sequence.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C, wherein The patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, and the product further comprises a third anti-HCV drug selected from: HCV polymerase inhibitor agents, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C For use, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and mixed thereof, the product further comprises a third anti-HCV drug, the third anti-HCV drug is selected from: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein The patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, and the product further comprises a third anti-HCV drug selected from: HCV polymerase inhibitor agents, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C For use, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and mixed thereof, the product further comprises a third anti-HCV drug, the third anti-HCV drug is selected from: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein The patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, and the product further comprises a third anti-HCV drug selected from: HCV polymerase inhibitor agents, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C For use, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and mixed thereof, the product further comprises a third anti-HCV drug, the third anti-HCV drug is selected from: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C, wherein Said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, said product further comprises a third anti-HCV drug selected from: HCv aggregate Enzyme inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C For use, wherein said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, said product further comprises a third anti-HCV drug selected from From: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein Said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, said product further comprises a third anti-HCV drug selected from: HCV Polymer Enzyme inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C For use, wherein said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, said product further comprises a third anti-HCV drug selected from From: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C, wherein Said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, said product further comprises a third anti-HCV drug selected from: HCV Polymer Enzyme inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C For use, wherein said patient is infected with HCV genotype 1 and said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b, said product further comprises a third anti-HCV drug selected from From: HCv polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, Used separately or sequentially, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), and the product also contains a third anti-HCV drug, so The third anti-HCV drug is selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, oncostatin M, and its combination.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for use as an anti-hepatitis C virus (HCV ) drugs are used simultaneously, separately or sequentially, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), and the product also contains a third antibody HCV drug, the third anti-HCV drug is selected from: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophins, tumor suppressors Prime M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for use as an anti-hepatitis C virus (HCV) drug simultaneously, Used separately or sequentially, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), and the product also contains a third anti-HCV drug, so The third anti-HCV drug is selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, oncostatin M, and its combination.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for use as an anti-hepatitis C virus (HCV ) drugs are used simultaneously, separately or sequentially, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), and the product also contains a third antibody HCV drug, the third anti-HCv drug selected from: HCv polymerase inhibitors, HCv protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophins, tumor suppressors Prime M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as an anti-hepatitis C virus (HCV) drug simultaneously, Used separately or sequentially, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), and the product also contains a third anti-HCV drug, so The third anti-HCV drug is selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, oncostatin M, and its combination.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as an anti-hepatitis C virus (HCV ) drugs are used simultaneously, separately or sequentially, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), and the product also contains a third antibody HCV drug, the third anti-HCV drug is selected from: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophins, tumor suppressors Prime M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, Used separately or sequentially, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from Genotypes of CC, CT and TT (preferably CT or TT), the product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, HCV life cycle Inhibitors of another target, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for use as an anti-hepatitis C virus (HCV ) drugs are used simultaneously, separately or sequentially, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, wherein the patient has a single nucleotide polymorphism on chromosome 19q13 rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT), said product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors , an inhibitor of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for use as an anti-hepatitis C virus (HCV) drug simultaneously, Used separately or sequentially, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from Genotypes of CC, CT and TT (preferably CT or TT), the product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, HCV life cycle Inhibitors of another target, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for use as an anti-hepatitis C virus (HCV ) drugs are used simultaneously, separately or sequentially, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, wherein the patient has a single nucleotide polymorphism on chromosome 19q13 rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT), said product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors , an inhibitor of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as an anti-hepatitis C virus (HCV) drug simultaneously, Used separately or sequentially, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a HCV genotype selected from Genotypes of CC, CT and TT (preferably CT or TT), the product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, HCV life cycle Inhibitors of another target, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as an anti-hepatitis C virus (HCV ) drugs are used simultaneously, separately or sequentially, wherein the patient is infected with HCV genotypes selected from 1, 2, 3, 4, 5, 6 and their mixture, wherein the patient has a single nucleotide polymorphism on chromosome 19q13 rs12979860 has a genotype selected from CC, CT and TT (preferably CT or TT), said product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors , an inhibitor of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, Separately or sequentially, wherein the patient is infected with HCV genotype 1 selected from 1a, 1b and mixed 1a/1b, wherein the patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 selected from CC, CT and genotype of TT (preferably CT or TT), the product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, another target in the HCV life cycle Inhibitors of , as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for use as an anti-hepatitis C virus (HCV ) drugs are used simultaneously, separately or sequentially, wherein the patient is infected with HCV genotype 1 selected from 1a, 1b and mixed 1a/1b, wherein the patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 selected from Genotypes of CC, CT and TT (preferably CT or TT), the product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, HCV life cycle Inhibitors of another target, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for use as an anti-hepatitis C virus (HCV) drug simultaneously, Separately or sequentially, wherein the patient is infected with HCV genotype 1 selected from 1a, 1b and mixed 1a/1b, wherein the patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 selected from CC, CT and genotype of TT (preferably CT or TT), the product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, another target in the HCV life cycle Inhibitors of , as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for use as an anti-hepatitis C virus (HCV ) drugs are used simultaneously, separately or sequentially, wherein the patient is infected with HCV genotype 1 selected from 1a, 1b and mixed 1a/1b, wherein the patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 selected from Genotypes of CC, CT and TT (preferably CT or TT), the product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, HCV life cycle Inhibitors of another target, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as an anti-hepatitis C virus (HCV) drug simultaneously, Separately or sequentially, wherein the patient is infected with HCV genotype 1 selected from 1a, 1b and mixed 1a/1b, wherein the patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 selected from CC, CT and genotype of TT (preferably CT or TT), the product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, another target in the HCV life cycle Inhibitors of , as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as an anti-hepatitis C virus (HCV ) drugs are used simultaneously, separately or sequentially, wherein the patient is infected with HCV genotype 1 selected from 1a, 1b and mixed 1a/1b, wherein the patient has a single nucleotide polymorphism rs12979860 on chromosome 19q13 selected from Genotypes of CC, CT and TT (preferably CT or TT), the product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, HCV life cycle Inhibitors of another target, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or simultaneous use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Used sequentially, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, the product further comprises a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or Used sequentially, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, the product further comprises a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as anti-HCV drug simultaneously, separately or in treatment-experienced patients with chronic hepatitis C Used sequentially, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, the product further comprises a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or simultaneous use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Sequential use, wherein the patient is infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixtures thereof, wherein the treatment-experienced patient is selected from non-responders, partial responders, relapsers and those who rebound during treatment, the product further comprises a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and Immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or Sequential use, wherein the patient is infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixtures thereof, wherein the treatment-experienced patient is selected from non-responders, partial responders, relapsers and those who rebound during treatment, the product further comprises a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and Immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as anti-HCV drug simultaneously, separately or in treatment-experienced patients with chronic hepatitis C Sequential use, wherein the patient is infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6, and mixtures thereof, wherein the treatment-experienced patient is selected from non-responders, partial responders, relapsers and those who rebound during treatment, the product further comprises a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and Immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or simultaneous use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Sequential use, wherein the patient is infected with HCV genotype 1 selected from 1a, 1b, and mixed 1a/1b, wherein the treatment-experienced patient is selected from non-responders, partial responders, relapsers, and treatment rebound Alternatively, the product further comprises a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, Antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or Sequential use, wherein the patient is infected with HCV genotype 1 selected from 1a, 1b, and mixed 1a/1b, wherein the treatment-experienced patient is selected from non-responders, partial responders, relapsers, and treatment rebound Alternatively, the product further comprises a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, Antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as anti-HCV drug simultaneously, separately or in treatment-experienced patients with chronic hepatitis C Sequential use, wherein the patient is infected with HCV genotype 1 selected from 1a, 1b, and mixed 1a/1b, wherein the treatment-experienced patient is selected from non-responders, partial responders, relapsers, and treatment rebound Alternatively, the product further comprises a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, Antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or simultaneous use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Sequential use, wherein said patient has a genotype selected from the group consisting of CC, CT and TT (preferably CT or TT) at the single nucleotide polymorphism rs12979860 on chromosome 19q13, wherein said treatment-experienced patient is selected from non-responders, For partial responders, relapsers, and those who rebound during treatment, the product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, another drug in the HCV life cycle Inhibitors of targets, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or Sequential use, wherein said patient has a genotype selected from the group consisting of CC, CT and TT (preferably CT or TT) at the single nucleotide polymorphism rs12979860 on chromosome 19q13, wherein said treatment-experienced patient is selected from non-responders, For partial responders, relapsers, and those who rebound during treatment, the product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, another drug in the HCV life cycle Inhibitors of targets, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as anti-HCV drug simultaneously, separately or in treatment-experienced patients with chronic hepatitis C Sequential use, wherein said patient has a genotype selected from the group consisting of CC, CT and TT (preferably CT or TT) at the single nucleotide polymorphism rs12979860 on chromosome 19q13, wherein said treatment-experienced patient is selected from non-responders, For partial responders, relapsers, and those who rebound during treatment, the product also contains a third anti-HCV drug selected from: HCV polymerase inhibitors, HCV protease inhibitors, another drug in the HCV life cycle Inhibitors of targets, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or simultaneous use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Use in sequence, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), wherein the patient is infected with a gene selected from 1, 2, 3, 4, 5, 6 and mixed HCV genotypes thereof, wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, said product further comprising a third anti-HCV drug, The third anti-HCV drug is selected from: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or Use in sequence, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), wherein the patient is infected with a gene selected from 1, 2, 3, 4, 5, 6 and mixed HCV genotypes thereof, wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, said product further comprising a third anti-HCV drug, The third anti-HCV drug is selected from: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as anti-HCV drug simultaneously, separately or in treatment-experienced patients with chronic hepatitis C Use in sequence, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT), wherein the patient is infected with a gene selected from 1, 2, 3, 4, 5, 6 and mixed HCV genotypes thereof, wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, said product further comprising a third anti-HCV drug, The third anti-HCV drug is selected from: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or simultaneous use as anti-HCV drugs in treatment-experienced patients with chronic hepatitis C Sequential use, wherein the patient has a genotype selected from the group consisting of CC, CT and TT (preferably CT or TT) with the single nucleotide polymorphism rs12979860 on chromosome 19q13, wherein the patient is infected with a group selected from 1a, 1b and mixed HCV genotype 1 of 1a/1b, wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, said product further comprises a third anti-HCV drug, said third Anti-HCV drugs are selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or Sequential use, wherein the patient has a genotype selected from the group consisting of CC, CT and TT (preferably CT or TT) with the single nucleotide polymorphism rs12979860 on chromosome 19q13, wherein the patient is infected with a group selected from 1a, 1b and mixed HCV genotype 1 of 1a/1b, wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, said product further comprises a third anti-HCV drug, said third Anti-HCV drugs are selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

In another embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for use as anti-HCV drug simultaneously, separately or in treatment-experienced patients with chronic hepatitis C Sequential use, wherein the patient has a genotype selected from the group consisting of CC, CT and TT (preferably CT or TT) with the single nucleotide polymorphism rs12979860 on chromosome 19q13, wherein the patient is infected with a group selected from 1a, 1b and mixed HCV genotype 1 of 1a/1b, wherein said treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders, said product further comprises a third anti-HCV drug, said third Anti-HCV drugs are selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors, inhibitors of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

Further embodiments of the present invention are those described above for the product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C , which also includes a third anti-HCV drug, the third anti-HCV drug is selected from: interferon α-2a, pegylated interferon α-2a, pegylated interferon α-2b, compound interferon, Purified interferon alpha product, or its recombinant form.

Further embodiments of the present invention are those described above for the product comprising IFN-α5 and IFN-α2a as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C , which also includes a third anti-HCV drug, the third anti-HCV drug is selected from: interferon α-2a, pegylated interferon α-2a, pegylated interferon α-2b, compound interferon, Purified interferon alpha product, or its recombinant form.

Further embodiments of the present invention are those described above for the product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use as anti-HCV drugs in patients with chronic hepatitis C , which also includes a third anti-HCV drug, the third anti-HCV drug is selected from: interferon α-2a, pegylated interferon α-2a, pegylated interferon α-2b, compound interferon, Purified interferon alpha product, or its recombinant form.

Further embodiments of the present invention are those mentioned above with regard to the product comprising IFN-α5 and IFN-α2 as a combined preparation for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C simultaneously, Used separately or sequentially, it also comprises a third anti-HCV drug selected from the group consisting of interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, Conjugated interferon, purified interferon alpha product, or a recombinant form thereof.

Further embodiments of the present invention are those mentioned above with regard to the product comprising IFN-α5 and IFN-α2a as a combined preparation for use as an anti-HCV drug simultaneously, Used separately or sequentially, it also comprises a third anti-HCV drug selected from the group consisting of interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, Conjugated interferon, purified interferon alpha product, or a recombinant form thereof.

Further embodiments of the present invention are those mentioned above with regard to the product comprising IFN-α5 and IFN-α2b as a combined preparation for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C simultaneously, Used separately or sequentially, it also comprises a third anti-HCV drug selected from the group consisting of interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, Conjugated interferon, purified interferon alpha product, or a recombinant form thereof.

Some preferred embodiments of the present invention are those mentioned above regarding the product comprising IFN-α5 and IFN-α2b as a combined preparation for use as an anti-HCV drug in treatment-experienced patients with chronic hepatitis C simultaneously, Used separately or sequentially, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use in the treatment of a patient infected with HCV, characterized in that HCV is genotype 1.

In one embodiment, the present invention relates to a composition comprising IFN-α5 and IFN-α2b for use in the treatment of a patient infected with HCV, characterized in that the single nucleotide polymorphism rs12979860 on chromosome 19q13 of said patient has selected Genotype from CC, CT and TT (preferably CT or TT).

Another embodiment of the present invention relates to the composition comprising IFN-α5 and IFN-α2b according to any one of the preceding two paragraphs, wherein said HCV infection is chronic.

Another embodiment of the present invention relates to the composition comprising IFN-α5 and IFN-α2b according to any one of the preceding three paragraphs, wherein said patient is a treatment experienced patient.

Another embodiment of the present invention relates to the composition comprising IFN-α5 and IFN-α2b according to the preceding paragraphs, wherein said treatment-experienced patients are selected from the group consisting of non-responders, partial responders, relapsers and treated rebounder.

Another embodiment of the present invention relates to the composition comprising IFN-α5 and IFN-α2b according to any one of the preceding five paragraphs, wherein said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b .

Another embodiment of the present invention relates to the composition comprising IFN-α5 and IFN-α2b according to any one of the preceding six paragraphs, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW, and the The dose of IFN-α2b administered is about 1.5 MIU, TIW.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use in the treatment of patients infected with hepatitis C virus (HCV), which Characterized by HCV genotype 1.

In one embodiment, the present invention relates to a product comprising IFN-α5 and IFN-α2b as a combined preparation for simultaneous, separate or sequential use in the treatment of patients infected with hepatitis C virus (HCV), which It is characterized in that the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT (preferably CT or TT).

Another embodiment of the present invention relates to a product according to any one of the preceding two paragraphs, wherein said HCV infection is chronic.

Another embodiment of the present invention relates to a product according to any one of the preceding three paragraphs, wherein said patient is a treatment experienced patient.

Another embodiment of the present invention relates to the product according to the preceding paragraph, wherein said treatment-experienced patients are selected from the group consisting of non-responders, partial responders, relapsers and treatment rebounders.

Another embodiment of the present invention relates to the product according to any one of the preceding five paragraphs, wherein said HCV genotype 1 is selected from 1a, 1b and mixed 1a/1b.

Another embodiment of the present invention relates to the product according to any one of the preceding six paragraphs, further comprising a third anti-HCV drug selected from the group consisting of: HCV polymerase inhibitors, HCV protease inhibitors , an inhibitor of another target in the HCV life cycle, and immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof.

Another embodiment of the present invention relates to the product according to the preceding paragraph, wherein said third anti-HCV drug is selected from the group consisting of: interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, consensus interferon, purified interferon alpha product, or a recombinant form thereof.

Another embodiment of the present invention relates to the product according to any one of the preceding eight paragraphs, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW and said IFN-α2b is administered at a dose of about 1.5 MIU , TIW.

To practice the present invention, a patient as defined in any one of the above embodiments is administered a sufficient and effective amount of IFN-α5 and IFN-α2a or IFN-α2b (preferably IFN-α2b) and optionally the third anti-HCV drug described above.

For administration purposes, IFN-α5, IFN-α2a and IFN-α2b can be formulated in various pharmaceutical forms. All compositions commonly used for systemically administering drugs can be employed as suitable compositions. Combining an effective amount of IFN-α5, IFN-α2a or IFN-α2b (preferably IFN-α2b) and the optional third anti-HCV drug as an active ingredient with a pharmaceutically acceptable carrier in intimate admixture To prepare the pharmaceutical compositions of the invention, the carrier can take a wide variety of forms depending on the desired mode of preparation for administration. These pharmaceutical compositions are expected to be in single dosage form particularly suitable for oral, rectal, transdermal, inhalation or parenteral routes (ie subcutaneous, intravenous, intramuscular or intraperitoneal). IFN-α5, IFN-α2a or IFN-α2b and optional third anti-HCV drug can be administered by oral route in solid dosage form such as tablet, capsule and powder, said liquid dosage form Examples are elixirs, syrups and suspensions. The pharmaceutical compositions of this invention can also be administered parenterally in sterile liquid dosage forms. Preferred routes of administration are those of the parenteral route, especially intramuscular, intravenous or subcutaneous injection.

Preparations for parenteral administration may be in the form of aqueous or non-aqueous isotonic sterile injections 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 liquid carriers, suspending agents and the like may be employed as appropriate. Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations. In compositions suitable for transdermal administration, the carrier optionally comprises a penetration enhancer and/or a suitable wetting agent, optionally in combination with minor proportions of suitable additives of any nature which are not irritating to the skin. cause significant toxicity. These said suitable additives may be antioxidants, preservatives, stabilizers, emulsifiers, salts for influencing the osmotic pressure, and/or buffer substances.

Alternatively, IFN-[alpha]5, IFN-[alpha]2a or IFN-[alpha]2b (preferably IFN-[alpha]2b) and optionally a third anti-HCV drug can be formulated in liposomes for delivery to epithelial cells. Liposomes can be prepared using conventional techniques, including sonication, chelate dialysis, homogenization, solvent infusion combined with extrusion, freeze-thaw extrusion, microemulsion, and the like. Reagents for cross-linking liposomes or other lipid-containing reagents to proteins of the invention include phospholipid derivatives that anchor one end of the cross-link in the lipid layer to a reactive group at the other to provide a point of attachment for a target biomolecule . Polymeric liposomes or liposomes coated with polymers can also be used. Such polymers can stabilize liposomes, reduce their clearance from the body, and/or reduce their immunogenicity. Liposomes can be loaded with functional moieties, such as diagnostic or therapeutic agents, during or after formation. These agents can be contained within the aqueous core of the liposome or can be incorporated or attached to the membrane surrounding it.

It is especially advantageous to formulate the aforementioned pharmaceutical compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein 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. Examples of such unit dosage forms are tablets (including scored or coated tablets), capsules, pills, suppositories, powder packets, wafers, injections or Suspensions, etc., and separate multiple forms thereof.

The daily dosage of the compounds of this invention will vary depending on the mode of administration, the desired treatment and the severity of the condition.

Generally, an effective amount of IFN-α5 is expected to be a dose of 1 MIU to 10 MIU three times a day or week, preferably 1 MIU to 5 MIU three times a day or week, more preferably 3 MIT three times a week. When IFN-α5 is administered in combination with interferon α-2b, it is preferably administered at a dose of 1.5 MIU, TIW, and interferon α-2b is administered at a dose of about 1.5 MIU, TIW.

IFNα2a is typically administered at 11.1 μg/0.5 mL, 22.2 μg/0.5 mL, 33.3 μg/0.5 mL 3 times daily or weekly. IFNα2b is typically administered at 0.038 mg/1 mL, 0.069 mg/1 mL, 0.087 mg/1.5 mL, 0.144 mg/1.5 mL, 0.192 mg/1 mL, 0.288 mg/1.5 mL by injection 3 or 5 times a week. IFNβla is typically administered as 8.8 μg/0.5 mL, 22 μg/0.5 mL or 44 μg/0.5 mL subcutaneously 3 times per week. IFNβ1b is typically administered as 0.0625 mg/0.25 mL and increasing to 0.25 mg/1 mL every other day subcutaneously.

The recommended dose of INTRON-A interferon alpha 2b (commercially available from Schering-Plough Corp.) is administered as subcutaneous injection at 3 MIU (12 micrograms)/0.5 mL/ITW for 24 weeks or 48 weeks on first treatment. The recommended dose of pegylated PEG-INTRON interferon alfa 2b (commercially available from Schering-Plough Corp.) is administered as subcutaneous injection at 1.5 micrograms/kg/week (in the range of 40 micrograms/week to 150 micrograms/week) Do it for at least 24 weeks. The recommended dose of ROFERON A interferon alfa 2a (commercially available from Hoffmann-La Roche) as administered at 3 MIU (11.1 micrograms/mL)/TIW subcutaneously or intramuscularly for at least 48 weeks to 52 weeks, or 6 MIU/TIW for 12 weeks, Followed by 3MIU/TIW for 36 weeks. The recommended dose of pegylated PEGASUS interferon alfa 2a (commercially available from Hoffmann-La Roche) is administered once weekly as a subcutaneous injection of 180 micrograms/1 mL or 180 micrograms/0.5 mL for at least 24 weeks. Recommended doses of INFERGEN interferon alfa-1 (commercially available from Amgen) as administered as subcutaneous injection at 9 micrograms/TIW for 24 weeks at first treatment and up to 15 micrograms/TIW for 24 weeks in non-responsive or relapsed treatment week. Optionally, ribavirin, a synthetic nucleoside analog with activity against a broad spectrum of viruses, including HCV, may be included in combination with IFN-α5 and IFN-α2b. The recommended dose of ribavirin is 600 mg/day to 1400 mg/day for at least 24 weeks (available as Rebetol ribavirin from Schering-Plough or Copegus ribavirin from Hoffmann-La Roche).

It may be appropriate to administer the required dose as one, two, three, four or more sub-doses at appropriate intervals throughout the day. Furthermore, it is evident that said effective daily dosage may be lowered or increased depending on the response of the treated subject and/or according to the evaluation of the physician prescribing the compounds of the invention. Therefore, effective daily doses within the above ranges herein are guidelines only.

The following examples are intended to illustrate the invention, not to limit it.

Example

The following are based on international standards of good clinical practice (International Conference on Harmonized Guidelines), applicable government regulations, local research policies and procedures, and according to the standard operating procedure (SOP) of the Contract Research Organization (CRO). ) Summary of the protocol and results of the human survey study conducted. Information about study subjects was kept confidential and managed in accordance with local legal requirements on subject data protection (Ley Orgánica 15/1999, de 13 de Diciembre, de Protección de Datos de Carácter Personal, Spain).

A randomized, open-label, active controlled, multicentre trial, phase I/II, involving treatment-experienced relapser patients with genotype 1 CHC infection was conducted. Clinical endpoints of the study involving the comparison of the antiviral efficacy of the three groups:

- Group A: IFN-α5 was administered subcutaneously in monotherapy at an initial dose of 3 MIU, 3 times a week for 29 days;

- Group B: IFN-α5 + IFN-α2b in combination therapy at the same total dose of 3 MIU (divided into equal doses of 1.5 MIU of IFN-α5 and 1.5 MIU of IFN-α2b), subcutaneously administer each agent weekly 3 sessions for 29 days; and

- Group C (control group): IFN-α2b was administered subcutaneously in monotherapy at a dose of 3 MIU, 3 times a week for 29 days. The efficacy of IFN-α2b relative to placebo in achieving SVR in patients infected with CHC has been demonstrated.

The selection of patients for clinical studies was based on the following inclusion criteria:

- Patients aged ≥18 years.

- Diagnosed with chronic hepatitis C (CHC) by being seropositive for anti-HCV antibodies or detectable HCV-RNA at least 6 months prior to screening.

- Patients with CHC infection of genotype 1 (1a, 1b or mixed 1a/1b) confirmed by genotype screening test.

- Defined as relapsers: who have achieved a viral response (undetectable HCV-RNA) at any time during standard of care treatment for CHC with IFN-α2 or PegIFN-α2+ribavirin, and who have achieved a virological response (undetectable HCV-RNA) at any time until the end of treatment at week 48 Those CHC patients who retained viral response at the time, but had HCV-RNA detection before 6 months after treatment.

- Patients with cirrhosis excluded by fiber scan or liver biopsy within 24 months prior to study inclusion.

- Serum HCV viral load ≥ 100.000 IU/mL at screening.

- Alanine transaminase (ALT) and aspartate transaminase (AST) serum measurements less than 5 times their upper limit of normal (ULN) at screening.

- Body Mass Index (BMI) of at least 18kg/m2 but not more than 36kg/m2.

- For female subjects of childbirth: use a known highly effective method of birth control defined as resulting in a low failure rate (i.e., less than 1 %/year): Birth control pills, IUDs, implants, partner vasectomy, or abstinence.

- For male subjects whose partners are likely to give birth: use an appropriate method of contraception (vasectomy, condom, or abstinence) for at least the duration of the study and for one month after the end of the study.

- Ability to communicate effectively with investigators and other test center personnel.

- Able to participate and willing to provide informed consent and comply with study restrictions.

Withdrawal of patients from clinical studies was based on the following exclusion criteria:

- Hepatitis C infection with genotype 2, 3 or 4 or any mixed genotype (1/2, 1/3 and 1/4) diagnosed by genotype screening test.

- Positive ELISA for HIV-1 or HIV-2.

- Hepatitis B virus (HBV) infection based on the presence of HBsAg.

- Decompensated liver disease, or history of decompensated liver disease as evidenced by ascites, portal hypertension, jaundice or hepatic encephalopathy, coagulopathy, varicose veins, history of variceal bleeding, or any history of decompensation other clinical evidence.

- With decompensated renal disease, immune-mediated disease, chronic lung disease, heart disease, thyroid disease, severe retinopathy, severe mental illness, organ transplant, cancer, seizure disorder, or pancreatitis Relevant medical history or other evidence of a medical condition.

- History of malignancy or active or suspected malignancy (other than appropriately treated basal cell carcinoma or carcinoma in situ of the cervix) within the last 5 years.

- Patients with a documented history of abstinence from drugs and alcohol for at least 12 months who are unlikely to relapse from the investigator's point of view may be included in the study.

- At screening, have a positive result for substance abuse.

- Females with hemoglobin <12.0 g/dL, and males with hemoglobin <13.0 g/dL at screening.

- White blood cell count <2000 cells/mm3 at Screening.

- Absolute neutrophil count <1500 cells/mm3 at Screening.

- Platelet count <100.000 cells/mm3 at screening.

- ALT and AST levels ≥ 5 x ULN at Screening.

- Prolongation to a prothrombin time INR (International Normalized Ratio) of 1.5 x ULN at Screening.

- At screening, TSH, T4 outside normal limits and thyroid function is not adequately controlled, patients with TSH below the lower limit of normal can be included if free T4 is normal and there is no clinical evidence of hyperthyroidism or hypothyroidism.

- Poorly controlled diabetes mellitus as evidenced by HbA1c >7.5% at screening.

- an alpha-fetoprotein (alfa-fetoprotein) value > 100 ng/mL at screening. If >20 ng/mL and <100 ng/mL, OK if no evidence of HCC on two appropriate imaging studies (e.g., ultrasound, CT scan, MRI) within 6 months of first visit Include patients.

- At screening, total bilirubin > 1.5 x ULN, direct/indirect ratio > 1 unless predominantly conjugated and reflecting Gilbert's disease.

- Estimated creatinine clearance of 30 mL/min or less at Screening.

- Women with confirmed pregnancy.

- People who have participated in another clinical trial within the past 4 weeks or are known to be highly sensitive to any component of the reagent under investigation.

- Patients at risk of bleeding (NSAID therapy, anticoagulant therapy, vitamin K deficiency, known coagulopathy, hemophilia).

- Hemoglobinopathies (eg, thalassemia major or sickle cell anemia).

- Screening ECG QTc value ≥ 450 ms and/or clinically significant ECG findings.

- History of clinically significant drug allergy.

- Participation in a clinical study with investigational drug, biologic, or device within 3 months prior to intended administration.

- Any chronic viral (including HSV), bacterial, mycobacterial, fungal, parasitic, or protozoan infection.

- Requires chronic systemic corticosteroids. Nasal or pulmonary steroids will be permitted.

- Receiving systemic antiviral, hematopoietic growth factor, or immunomodulatory therapeutics within 30 days prior to enrollment.

The study sponsor Digna Biotech (Spain) provided interferon-α5 in 1.0 mL prefilled syringes prepared by Rentschler Biotechnologie GmbH (Germany) for administration to selected patients as a solution for subcutaneous injection. One syringe contains 9MIU/0.6mi of solution for injection which is 3MIU in 0.2mL.

The administered interferon-α5 is recombinant human protein IFN-α5, 167 amino acids in length, and the sequence is (SEQ ID NO3):

MCDLPQTHSLSNRRTLMIMAQMGRISPFSCLKDRHDFGFPQEEFDGNQFQKAQAISVLH

EMIQQTFNLFSTKDSSATWDETLLDKFYTELYQQLNDLEACMMQEVGVEDTPLMNVDS

ILTVRKYFQRITLYLTEKKYSPCAWEVVRAEIMRSFSLSANLQERLRRKE.

Interferon-α2b in a 1.5 mL multi-dose pen for injection was provided by the study sponsor Digna Biotech (Spain) as a solution for subcutaneous injection It was obtained from Shering Plow (USA). One pen has a strength of 3MIU and contains 6 doses, 0.2mL each, 3MIU in 0.2mL.

Eligible patients were randomized to one of three treatment groups at Visit-1. The CRO was the provider of randomization used in this trial. Patients were randomly assigned to the three available groups according to the study period.

To compare the antiviral efficacy of the three different treatments, the time-dependent reduction in viral load at day 29 relative to day 1 was measured for each group.

Viral load measurements were performed on patient serum samples obtained in each study. When appropriate, provide detailed instructions for obtaining, handling, and shipping samples for viral load measurement. Samples were processed by Central Laboratory Services using an assay with a lower limit of quantitation of 30 IU/mL.

Preliminary clinical data from human studies are shown in Tables 1, 2 and 3 below.

Table 1. Per protocol, patient, per treatment group

Treatment group, patient number, results of nucleotide sequence (CC, CT or TT) near the gene encoding IL28B, HCVLog-scale viral load on day 1 (before treatment) and day 29 of treatment, and each patient's Viral load is reduced.

Table 2 Each regimen, CT and TT patients, each treatment group

Treatment group, patient number, results of nucleotide sequence (CT or TT) near the gene encoding IL28B, HCVLog scale viral load on day 1 (before treatment) and day 29 of treatment, and viral load per patient reduce.

Table 3. CT and TT patients by regimen, grouped by monotherapy or combination therapy

Treatment group, patient number, results of nucleotide sequence (CT or TT) near the gene encoding IL28B, HCVLog scale viral load on day 1 (before treatment) and day 29 of treatment, and viral load per patient reduce.

Referring to Table 1, it was found that for patients with CC, CT, or TT nucleotide sequences in polymorphisms located in chromosome 19 (near the IL28B coding region), 6 out of 13 patients in treatment group A, Nine of 14 patients in Arm B and 5 of 14 patients in Treatment Arm C achieved a reduction in viral load on the scale of > 0.5 Log on Day 29 of treatment compared to Day 1 (before the start of treatment).

Referring to Table 2, it was found that for patients with a CT or TT nucleotide sequence in a polymorphism located in chromosome 19 (near the IL28B coding region), 2 out of 9 patients in treatment group A and 2 in treatment group B Six of 11 patients in the treatment arm C and 2 of the 11 patients in treatment arm C achieved a reduction in viral load on the scale of ≥ 0.5 Log on day 29 of treatment compared to day 1 (before the start of treatment).

Referring to Table 3, it was found that for patients with a CT or TT nucleotide sequence in a polymorphism located in chromosome 19 (near the IL28B coding region), combination therapy in group B (IFN-α5 and IFN-α2b) resulted in 11 Six of the patients achieved a viral load reduction of ≥0.5 Log scale on treatment day 29 compared to day 1 (before treatment initiation), compared to 20 patients in the monotherapy arms of Arms A and C Four of them achieved a ≥0.5 Log scale reduction in viral load on Day 29 of treatment compared to Day 1 (before treatment started). Responses between treatments were compared and proportional differences were estimated by 95% confidence intervals (Newcombe recommended method). The difference in proportions was 0.345, which was significant at the 0.05 level (95% confidence interval: 0.0033, 0.615).

See Table 3, in Group B (IFN-α5+IFN-α2b), the Log-scale change in HCV viral load was -0.67 (0.66) on Day 29 of treatment compared to Day 1 [mean (SD), n=11], compared to 0.27 (0.43) [mean (SD), n=20] for arms A and C monotherapy. Comparisons of means between treatments were performed using the Student-t test, with differences in means estimated by 95% confidence intervals. A minimally statistically significant difference was found when comparing treatment means (P=0.046).

Two-sided statistical tests were performed at a level of 0.05. All analyzes were performed with SAS9.3.

It was concluded that for patients with CT or TT nucleotide sequence polymorphisms located in polymorphisms located in chromosome 19 (close to the IL28B coding region), treatment B (ie, the combination of IFN-α5 + IFN-α2b) at Patients achieved greater than 0.5 Log reduction in HCV viral load on Day 29 of treatment and showed the best results in terms of overall reduction in viral load on Day 29 of treatment.

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Claims (26)

Claims 1. A composition comprising IFN-α5 and IFN-α2 for use as an anti-hepatitis C virus (HCV) drug in patients with chronic hepatitis C. 2. The composition of claim 1, wherein the patient is a therapy experienced patient. 3. The composition according to any one of claims 1 to 2, wherein IFN-α2 is selected from IFN-α2a and IFN-α2b. 4. The composition according to any one of claims 1 to 3, wherein the patient is infected with an HCV genotype selected from the group consisting of 1, 2, 3, 4, 5, 6 and mixtures thereof. 5. The composition of claim 4, wherein the HCV genotype 1 is selected from the group consisting of 1a, 1b and mixed 1a/1b. 6. The composition according to any one of claims 1 to 5, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT. 7. The composition according to any one of claims 2 to 6, wherein the treatment experienced patients are selected from the group consisting of non-responders, partial responders, relapsers and treatment rebounders. 8. The composition of any one of claims 3 to 7, wherein the IFN-α5 is administered at a dose of about 1.5 MIU, TIW and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW. 9. A product comprising IFN-α5 and IFN-α2 as a combined preparation for simultaneous, separate or sequential use as an anti-HCV drug in patients with chronic hepatitis C. 10. The product according to claim 9, wherein the patient is a treatment experienced patient. 11. The product according to any one of claims 9 to 10, wherein IFN-α2 is selected from IFN-α2a and IFN-α2b. 12. The product according to any one of claims 9 to 11, wherein the patient is infected with an HCV genotype selected from 1, 2, 3, 4, 5, 6 and mixtures thereof. 13. The product according to claim 12, wherein the HCV genotype 1 is selected from the group consisting of 1a, 1b and mixed 1a/1b. 14. The product according to any one of claims 9 to 13, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT. 15. The product according to any one of claims 10 to 14, wherein the treatment experienced patients are selected from the group consisting of non-responders, partial responders, relapsers and treatment rebounders. 16. The product according to any one of claims 9 to 15, further comprising a third anti-HCV drug selected from the group consisting of HCV polymerase inhibitors, HCV protease inhibitors, HCV life cycle Inhibitors of other targets, as well as immunomodulators, antiviral agents, cardiotrophin, Oncostatin M, and combinations thereof. 17. The product according to claim 16, wherein the third anti-HCV drug is selected from interferon alpha-2a, pegylated interferon alpha-2a, pegylated interferon alpha-2b, compound interferon , a purified interferon alpha product, or a recombinant form thereof. 18. The product according to any one of claims 11 to 17, wherein said IFN-α5 is administered at a dose of about 1.5 MIU, TIW and said IFN-α2b is administered at a dose of about 1.5 MIU, TIW. 19. A method of treating a patient with chronic hepatitis C comprising administering a therapeutically effective amount of IFN-[alpha]5 and IFN-[alpha]2. 20. The method of claim 19, wherein the patient is a therapy experienced patient. 21. The method according to any one of claims 19 to 20, wherein IFN-α2 is selected from IFN-α2a and IFN-α2b. 22. The method according to any one of claims 19 to 21, wherein the patient is infected with an HCV genotype selected from the group consisting of 1, 2, 3, 4, 5, 6 and mixtures thereof. 23. The method of claim 22, wherein the HCV genotype 1 is selected from la, lb and mixed la/lb. 24. The method according to any one of claims 19 to 23, wherein the single nucleotide polymorphism rs12979860 on chromosome 19q13 of the patient has a genotype selected from CC, CT and TT. 25. The method of any one of claims 20 to 24, wherein the treatment-experienced patients are selected from non-responders, partial responders, relapsers and treatment rebounders. 26. The method of any one of claims 21 to 25, wherein the IFN-α5 is administered at a dose of about 1.5 MIU, TIW and the IFN-α2b is administered at a dose of about 1.5 MIU, TIW.