+32 1658 9045
0032 (0)16 41 44 07
+32 1650 9045
Av. de l' Armée 68
tel 01 43 25 01 50
fax01 43 25 01 60
9, rue Lagrange
tel 02 36 00 65 93
fax 02 36 00 65 94
tel +32 1658 9045
fax +32 1650 9045
Tel 058 710 33 44
Fax 00 32 16 50 90 45
ul. Grunwaldzka 88A/2
tel +81 78 386 0860
fax +81 78 306 0296
Česká republika Praha
US New York
0032 (0)16 41 44 07
Pegylated Recombinant Human Interferon-alpha 2b (PEG-IFNα2b)
(Cat. No.: C007)
At least 23 different variants of Interferon-alpha are known. The individual proteins have molecular masses between 19-26 kDa and consist of proteins with lengths of 156-166 and 172 amino acids. All IFN-alpha subtypes possess a common conserved sequence region between amino acid positions 115-151 while the amino-terminal ends are variable. Many IFN-alpha subtypes differ in their sequences at only one or two positions. Naturally occurring variants also include proteins truncated by 10 amino acids at the carboxyl-terminal end.
Recombinant Human Interferon alpha-2b produced in E. coli is a single, non-glycosylated, polypeptide chain containing 165 amino acids and having a molecular mass of 19269 Dalton. Pegylated IFN alpha-2b is manufactured by attaching a 40KD NHS-mPEG to the primary amino acid of IFN alpha-2b.
Biological Activity: The specific activity as determined in a viral resistance assay using VSV-WISH cells was found to be 1.0 x 106 IU/mg.
Purity: Greater than 98.0% as determined by:
(a) Analysis by RP-HPLC.
(b) Anion-exchange FPLC.
(c) Analysis by reducing and non-reducing SDS-PAGE Silver Stained gel.
Amino acid sequence: The sequence of the first five N-terminal amino acids was determined and was found to be Met-Cys-Asp-Leu-Pro.
Endotoxin: Less than 0.1 ng/µg (IEU/µg) of PEG-IFN alpha-2b.
Formulation: Lyophilized from a (0.5mg/ml) solution in containing 8.8mg sodium chloride, 0.4mg sodium acetate and 1.0mg acetate acid buffer.
Storage: Lyophilized PEG-IFN alpha-2b although stable at room temperature for 3 weeks, should be stored desiccated below -18oC. Upon reconstitution PEG-IFN alpha-2b should be stored at 4oC between 2-7 days and for future use below -18oC. For long-term storage it is recommended to add a carrier protein (0.1% HSA or BSA).
Please avoid freeze-thaw cycles.
Reconstitution: It is recommended to reconstitute the lyophilized PEG-IFN alpha-2b in sterile 18MΩ-cm H2O not less than 100µg/ml, which can then be further diluted to other aqueous solutions.
1: Orv Hetil 2009 Jan;Vol 150(2)
[Effects of silymarin supplementation in chronic hepatitis C patients treated with peg-interferon + ribavirin. A placebo-controlled double blind study.]
[Abstract] Since oxidative stress may play a pathogenetic role in chronic hepatitis C, and sustained virological response to antiviral therapy is limited in HCV1 genotype infection, a double blind study was performed in HCV1 patients treated with pegylated interferon + ribavirin, to assess the efficacy of supplementation with the antioxidant flavonoid silymarin. Patients and methods: Thirty-two naive HCV1 positive patients with biopsy proven chronic hepatitis C, to be treated with pegylated interferon + ribavirin, have been randomized: group A): 16 patients have been given the antiviral therapy for 6-12 months plus placebo for the first 3 months; group B): 16 patients have been treated with pegylated interferon + ribavirin for 6-12 months plus silymarin, 2 x 166 mg/day,
was given for 3 months. Serum alanine aminotransferase and HCV-RNA levels as well as parameters of oxidative stress such as plasma or red blood cell hemolysate, malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase and myeloperoxidase were determined after 0, 1, 3, 6 and 12 months during the treatment. Sustained virological response as undetectable serum HCV RNA was evaluated 24 weeks after the end of therapy. Results: In the silymarin group, a more rapid decrease in the malondialdehyde level as well as a marked decrease in superoxide dismutase and an increase in myeloperoxidase activity after month 12 were found, alanine aminotransferase normalized in 6/16 (vs control 9/16) cases, and sustained virological response occurred in 3/16 (vs 7/16) patients.
Discussion/conclusion: Although silymarin supportation to antiviral therapy improved oxidative stress, it was able to affect favourably neither the alanine aminotransferase nor the sustained virological response. These contradictory findings may be related to randomization bias as patients in study group B had more negative predictors of response: they were older with higher fibrosis score and even with more severe pretreatment baseline oxidative stress. Regarding the recently published in vitro experiments with silybinin on HCV replication as well as the newest convincing clinical observations, we do suggest further studies with more than three times higher doses of silymarin in controlled trials to assess the value of this supplementation in antivirally treated HCV patients.
2: Hepatol Res 2008
Treatment of hepatitis C virus with peg-interferon and ribavirin combination therapy significantly affects lipid metabolism.
[Abstract] Aim: We investigated lipid metabolism in patients with chronic hepatitis C virus (HCV), serotype 1, undergoing combination therapy with PEG-IFN alpha-2b (PEG-IFN) and ribavirin (RBV). Methods: A total of 185 patients with chronic HCV (HCV serotype 1; HCV RNA levels >/= 100 KIU/mL) who received a combination of PEG-IFN and RBV were enrolled. Results: Sustained virological response (SVR) was obtained in 82 cases (44.3%). The median age, red blood cell and platelet counts differed significantly between the SVR and non-SVR groups before treatment. However there was no significant difference between total cholesterol (TC), LDL-cholesterol (LDL-C) and triglyceride (TG) levels before treatment. TC and LDL-C levels decreased during the treatment in both groups. In the
SVR group, TC and LDL-C levels increased quickly after the end of the treatment and were higher than those before treatment. On the other hand, TC and LDL-C levels returned to pretreatment levels in the non-SVR group and were significantly lower than in the SVR group. TG levels were elevated in both groups after the beginning of treatment. After the end of treatment, this elevation persisted in the SVR group, while TG levels returned to pre-treatment levels in the non-SVR group. There was a significant difference in TG levels at 24 weeks after the end of the treatment between the 2 groups. In the non-SVR group some patients achieved normalization of ALT (alanine aminotransferase) but persistence of normal ALT levels did not contribute to the increase of TC and TG. Conclusion: TC, LDL-C and
TG levels increase only in patients with HCV, serotype 1, undergoing combination therapy when a SVR is achieved.
3: J Chemother 2008 Oct;Vol 20(5)
Bone marrow toxicity in HCV genotype 5a-infected patient after peg-IFN alpha-2a and ribavirin therapy.
[Abstract] The optimal therapy for HCV-related chronic hepatitis is the combination of pegylated interferon alpha (peg-IFN alpha) plus ribavirin (RBV). Unfortunately, both peg-IFN alpha and RBV are responsible for a wide range of adverse events and potentially severe toxicities, particularly hematological alterations. Indeed, RBV is generally responsible for anemia through hemolysis, while peg-IFN alpha induces more commonly leukopoenia and thrombocytopenia, presumably through bone marrow toxicity. Actually, data regarding histopathological bone marrow alterations in HCV-infected patients following IFN-alpha therapy is scanty. We report a case of a HCV-infected cirrhotic patient, who developed bone marrow alterations following one-year peg-IFN alpha plus RBV treatment,
and we describe the associated histopathological features. Our case report provides new significant insight on the histopathological changes occurring in bone marrow of HCV-infected cirrhotic patients during peg-IFN alpha-2a plus RBV treatment, providing also additional information on potential bone marrow toxicity in the course of IFN-based treatments.
4: J Transl Med 2008 ;Vol 6
Cyclic changes in gene expression induced by Peg-interferon alfa-2b plus ribavirin in peripheral blood monocytes (PBMC) of hepatitis C patients during the first 10 weeks of treatment.
[Abstract] BACKGROUND AND AIMS: This study determined the kinetics of gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntron) and ribavirin (administered by weight) in HCV patients and compared it with the recently completed Virahep C study 12 in which Peginterferon-alfa2a (Pegasys) and ribavirin were administered. METHODS: RNA was isolated from peripheral blood monocytes (PBMC) from twenty treatment-na?ve patients just before treatment (day 1) and at days 3, 6, 10, 13, 27, 42 and 70 days after treatment. Gene expression at each time was measured using Affymetrix microarrays and compared to that of day 1. RESULTS: The expression of many genes differed significantly (p <or= 0.001 and changed at least 1.5-fold) at days 3 (290
probes) and 10 (255 probes), but the number dropped at days 6 (165) and 13 (142). Most genes continued to be up regulated throughout the trial period. A second group of genes, including CXCL10, CMKLR1 (chemokine receptor 1), TRAIL, IL1Ralpha and genes associated with complement and lipid metabolism, was transiently induced early in treatment. CDKN1C (cyclin kinase inhibitor 1) was induced early but repressed at later times. Genes induced at later times were mostly related to blood chemistry and oxygen transport. By week 10, 11 of the patients demonstrated a positive response to therapy, and the final sustained viral response (SVR) was 35%. The levels of gene induction or decrease was very similar to that previously reported with Pegasys/ribavirin treatment. CONCLUSION: The response to
Pegintron/ribavirin was similar to that reported for Pegasys/ribavirin despite some differences in the amount administered. We did not detect major differences at the genomic level between patients responding to treatment or non-responders, perhaps because of limited power. Gene induction occurred in a cyclic fashion, peaking right after administration of interferon and declining between administrations of the drug. Our data suggest that more than once a week dosing might be desirable early during treatment to maintain high levels of response as measured by gene expression.
Protein Accession No.:
MDLPQ THSLG SRRTL MLLAQ MRRIS LFSCL KDRHD FGFPQ EEFGN QFQKA ETIPV LHEMI QQIFN LFSTK DSSAA WDETL LDKFY TELYQ QLNDL EACVI QGVGV TETPL MKEDS ILAVR KYFQR ITLYL KEKKY SPCAW EVVRA EIMRS FSLST NLQES LRSKE
*NOTE: ALL PRODUCTS ARE FOR RESEARCH USE ONLY