{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:46:24Z","timestamp":1777452384471,"version":"3.51.4"},"reference-count":38,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2012,7,1]],"date-time":"2012-07-01T00:00:00Z","timestamp":1341100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study presents preclinical data of a novel interferon (IFN)-\u03b18 fusion protein, PF-04849285, and compares it with IFN-\u03b12 and pegylated IFN-\u03b12; the latter being the current standard of care for HCV.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The antiviral properties were evaluated in vitro using the HCV replication assay (replicon) and the general encephalomyocarditis virus assay. The binding affinity to both IFNR-subunits was assessed using surface plasmon resonance. Ex vivo experiments using cynomolgus monkey and human blood were used for the evaluation of induction of IFN-inducible biomarkers (interferon inducible protein 10 [IP-10], 2\u2032-5\u2032-oligoadenylate synthetase [OAS2] and interleukin-6 [IL-6]). The molecule was tested intravenously and subcutaneously in cynomolgus monkey in a single dose study for two weeks at 0.01, 1, 5 and 20 mg\/kg. Each route and dose combination was given to a single male animal, blood samples were collected for evaluation of biomarkers and pharmacokinetics. The compound was also tested in cynomolgus monkey in a multiple dose study for four weeks, with a twice-a-week dosing prior to a three-week wash-out period for toxicokinetics, pharmacokinetics, and biomarker evaluation at 20, 50 or 100 mg\/kg subcutaneously and 20 mg\/kg intravenously.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The molecule is 10x more potent than the pegylated IFN-\u03b12a, with potency similar to the unmodified IFN-\u03b12a. No unanticipated findings were observed in cynomolgus monkey when dosed up to 20 mg\/kg, &gt;10,000-fold margin over the anticipated efficacious human dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The biomarker and toxicological findings were consistent with a potent IFN molecule. The potency and pharmacokinetic properties of the molecule are consistent with dosing at least twice daily with the potential for monthly dosing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp2099","type":"journal-article","created":{"date-parts":[[2012,4,13]],"date-time":"2012-04-13T11:20:38Z","timestamp":1334316038000},"page":"869-881","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Preclinical Studies of Pf-04849285, An Interferon-\u03b18 Fusion Protein for the Treatment of HCV"],"prefix":"10.1177","volume":"17","author":[{"given":"M Victoria","family":"Flores","sequence":"first","affiliation":[{"name":"Antivirals Group, Pfizer Inc., Sandwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy P","family":"Hickling","sequence":"additional","affiliation":[{"name":"Translational Research, Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Sandwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sasha","family":"Sreckovic","sequence":"additional","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., Sandwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark D","family":"Fidock","sequence":"additional","affiliation":[{"name":"Quantitative Biomarkers Group, Pfizer Inc., Sandwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel","family":"Horscroft","sequence":"additional","affiliation":[{"name":"Antivirals Group, Pfizer Inc., Sandwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madan","family":"Katragadda","sequence":"additional","affiliation":[{"name":"BioTherapeutics Research, Pfizer Inc., Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boris","family":"Savic","sequence":"additional","affiliation":[{"name":"Antivirals Group, Pfizer Inc., Sandwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaiessh","family":"Rawal","sequence":"additional","affiliation":[{"name":"Translational Research, Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Sandwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oona E","family":"Delpuech-Adams","sequence":"additional","affiliation":[{"name":"Quantitative Biomarkers Group, Pfizer Inc., Sandwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Robas","sequence":"additional","affiliation":[{"name":"Quantitative Biomarkers Group, Pfizer Inc., Sandwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Corey","sequence":"additional","affiliation":[{"name":"Quantitative Biomarkers Group, Pfizer Inc., Sandwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Nelms","sequence":"additional","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., Groton, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Lawton","sequence":"additional","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., Groton, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Marcek","sequence":"additional","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., Groton, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makeida","family":"Stubbs","sequence":"additional","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., Groton, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Westby","sequence":"additional","affiliation":[{"name":"Antivirals Group, Pfizer Inc., Sandwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Ciaramella","sequence":"additional","affiliation":[{"name":"BioTherapeutics Research, Pfizer Inc., Sandwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2012,7,1]]},"reference":[{"key":"bibr1-IMP2099","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2008.10.035"},{"key":"bibr2-IMP2099","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22403"},{"key":"bibr3-IMP2099","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.06.062"},{"key":"bibr4-IMP2099","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(09)61043-6"},{"key":"bibr5-IMP2099","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.10.5255"},{"key":"bibr6-IMP2099","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(81)90195-8"},{"key":"bibr7-IMP2099","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(83)91498-5"},{"key":"bibr8-IMP2099","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.15.8219-8228.2004"},{"key":"bibr9-IMP2099","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2008.0037"},{"key":"bibr10-IMP2099","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(84)90105-3"},{"key":"bibr11-IMP2099","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-67-8-1633"},{"key":"bibr12-IMP2099","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2726"},{"key":"bibr13-IMP2099","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2893.1998.0050s1013.x"},{"key":"bibr14-IMP2099","doi-asserted-by":"publisher","DOI":"10.1089\/jir.1996.16.1027"},{"key":"bibr15-IMP2099","doi-asserted-by":"publisher","DOI":"10.1016\/j.hepres.2005.10.005"},{"key":"bibr16-IMP2099","doi-asserted-by":"publisher","DOI":"10.1089\/107999099312803"},{"key":"bibr17-IMP2099","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609001104"},{"key":"bibr18-IMP2099","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2008.0038"},{"key":"bibr19-IMP2099","unstructured":"Ciaramella G., Flores M.V., Horscroft N.J., Katragadda M., Wu J. inventors; Pfizer Limited, assignee. 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Toxicologist's review, BLA 99\u20131488\/103949. (Updated 19 December 2000. Accessed 27 September 2008.) 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