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Pittsboro, NC, United States

Dzyublyk I.,City Clinical Hospital 5 | Yegorova T.,City Clinical Hospital 5 | Moroz L.,Vinnitsa National Medical University | Popovych O.,Vinnitsa National Medical University | And 6 more authors.
Journal of Viral Hepatitis | Year: 2011

Better convenience and tolerability and sustained therapeutic concentrations might improve interferon (IFN) treatment for chronic hepatitis C virus (HCV) infection. In an open-label, randomized study, controlled release free (chemically unmodified) recombinant human IFN-α 2b in poly(ether-ester) microspheres (CR-rhIFN-α 2b), was injected at doses of 160, 320, 480 or 640 μg every 2 weeks for 12 weeks with concomitant weight-based oral ribavirin in 32 treatment-naïve patients with chronic HCV genotype 1. Treatment was well tolerated, with 31 patients (97%) successfully completing the study. Full doses of CR-rhIFN-α 2b were administered on 96% of scheduled occasions. Flu-like symptoms were generally mild and brief. Injection site reactions developed in 13 patients (41%), and neutropenia occurred in six of eight patients receiving 640 lg. In the 320, 480 and 640 μg groups, 62-75% of patients achieved a ≥2 log 10 HCV RNA reduction by 4 weeks and 88-100% by 12 weeks. For those groups, the pooled median time to ≥2 log10 reduction was 11 days (95% confidence interval, 7-35 days). In those groups, viral reduction below the limit of detection was accomplished in 25% of patients by 4 weeks and in 62% by 12 weeks. The 160-μg dose was less potent. After CR-rhIFN-α 2b injection, stable plateau levels of serum IFN-α 2b were generally reached within 72 h. Treatment-emergent neutralizing antibodies to IFN-α 2b were observed in one patient. No antibodies to host plant proteins were detected. CR-rhIFN-α 2b with ribavirin cotherapy was well tolerated and displayed potent early antiviral activity in patients with chronic HCV genotype 1. © 2010 Blackwell Publishing Ltd. Source


Patent
Biolex Therapeutics | Date: 2010-05-26

Compositions and methods for producing aglycosylated plasminogen (PLG) polypeptides and fragments and variants thereof are provided. Compositions of the invention include isolated nucleic acid molecules encoding aglycosylated PLG polypeptides in which the asparagine (Asn) residue corresponding to residue Asn-289 of the mature human PLG polypeptide has been substituted with an amino acid residue that does not support N-linked glycosylation at that position of the PLG polypeptide, as well as the aglycosylated PLG polypeptides encoded thereby. Expression constructs comprising these PLG-encoding nucleic acid molecules and transgenic plants comprising these expression constructs are also provided. Methods of the invention comprise introducing a PLG-encoding nucleic acid molecule of the invention into a plant of interest and culturing the plant under conditions to produce the aglycosylated PLG polypeptide. The aglycosylated PLG polypeptide allows for significant increases in production and yield of PLG from a plant-based expression system without comprising the ability of the PLG product to be activated to a polypeptide capable of binding fibrin and having serine protease activity, including biologically active plasmin that is also glycosylated. The activated aglycosylated plasmin is useful to treat diseases or conditions associated with a thrombus.


Gasdaska J.R.,Biolex Therapeutics | Sherwood S.,Aragen Bioscience | Regan J.T.,Biolex Therapeutics | Dickey L.F.,Biolex Therapeutics
Molecular Immunology | Year: 2012

The objective of this study was to characterize the in vitro and in vivo activity of a novel afucosylated rituximab (BLX-300) expressed in a Lemna aquatic plant-based system free of zoonotic pathogens. The glycosylation of BLX-300 was shown to be homogeneous, composed of a single major N-glycan species without detectable fucose or xylose. Target cell binding and induction of apoptosis were similar for BLX-300 and rituximab. Antibody-dependent cellular cytotoxicity (ADCC) was increased by BLX-300 versus rituximab in phenylalanine/phenylalanine (F/F), phenylalanine/valine (F/V) and valine/valine (V/V) genotype donors, as indicated by respective log reductions of 0.82, 1.07 and 0.92 in EC 50. BLX-300 also showed greater B-cell depletion than rituximab in whole blood from donors of F/F, F/V and V/V genotype in vitro and cynomolgus monkeys in vivo. Temporal changes in circulating levels of BLX-300 and rituximab were similar in cynomolgus monkeys. Complement-dependent cytotoxicity (CDC) was attenuated by BLX-300 relative to rituximab, as judged by a log increase of 0.51 in EC 50. The higher ADCC and B-cell depletion suggest a potential improvement in effectiveness and potency, while lower CDC may mitigate infusion toxicity. © 2012 Elsevier Ltd. Source


Bertran K.,U.S. Department of Agriculture | Thomas C.,U.S. Department of Agriculture | Guo X.,Merial Limited | Bublot M.,Merial SAS | And 7 more authors.
Vaccine | Year: 2015

A synthetic hemagglutinin (HA) gene from the highly pathogenic avian influenza (HPAI) virus A/chicken/Indonesia/7/2003 (H5N1) (Indo/03) was expressed in aquatic plant Lemna minor (rLemna-HA). In Experiment 1, efficacy of rLemna-HA was tested on birds immunized with 0.2μg or 2.3μg HA and challenged with 106 mean chicken embryo infectious doses (EID50) of homologous virus strain. Both dosages of rLemna-HA conferred clinical protection and dramatically reduced viral shedding. Almost all the birds immunized with either dosage of rLemna-HA elicited HA antibody titers against Indo/03 antigen, suggesting an association between levels of anti-Indo/03 antibodies and protection. In Experiment 2, efficacy of rLemna-HA was tested on birds immunized with 0.9μg or 2.2μg HA and challenged with 106 EID50 of heterologous H5N1 virus strains A/chicken/Vietnam/NCVD-421/2010 (VN/10) or A/chicken/West Java/PWT-WIJ/2006 (PWT/06). Birds challenged with VN/10 exhibited 100% survival regardless of immunization dosage, while birds challenged with PWT/06 had 50% and 30% mortality at 0.9μg HA and 2.2μg HA, respectively. For each challenge virus, viral shedding titers from 2.2μg HA vaccinated birds were significantly lower than those from 0.9μg HA vaccinated birds, and titers from both immunized groups were in turn significantly lower than those from sham vaccinated birds. Even if immunized birds elicited HA titers against the vaccine antigen Indo/03, only the groups challenged with VN/10 developed humoral immunity against the challenge antigen. None (rLemna-HA 0.9μg HA) and 40% (rLemna-HA 2.2μg HA) of the immunized birds challenged with PWT/06 elicited pre-challenge antibody titers, respectively. In conclusion, Lemna-expressed HA demonstrated complete protective immunity against homologous challenge and suboptimal protection against heterologous challenge, the latter being similar to results from inactivated whole virus vaccines. Transgenic duckweed-derived HA could be a good alternative for producing high quality antigen for an injectable vaccine against H5N1 HPAI viruses. © 2015. Source

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