{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:08:04Z","timestamp":1768867684787,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2018,10,27]],"date-time":"2018-10-27T00:00:00Z","timestamp":1540598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Olaratumab (Lartruvo\u2122) is a recombinant human IgG<jats:sub>1<\/jats:sub> monoclonal antibody that specifically binds PDGFR\u03b1. The maternal and in utero embryo\u2010fetal toxicity and toxicokinetics of a human anti\u2010mouse PDGFR\u03b1 antibody (LSN3338786) were investigated in pregnant mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A pilot study was used to set doses for the definitive study. In the definitive study, mice were administered vehicle, 5, 50, or 150\u2009mg\/kg LSN3338786 by intravenous injection on gestation days (GD) 6, 9, 12, and 15. Fetal tissues and\/or serum samples were collected on GD 10, 12, 15, and 18 to evaluate exposure of antibody.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were no adverse maternal effects at 50 and 150\u2009mg\/kg although maternal deaths and adverse clinical signs were observed at 5 mg\/kg. LSN3338786 crossed the placenta as early as GD 10 during organogenesis. Elimination half\u2010life of LSN3338786 in dams decreased between GD 6 and 15. On GD 18, fetal serum concentrations of antibody were substantially higher than maternal serum concentrations at all doses. Increased incidences of malformations consisting of open and partially open eye and increased incidences of skeletal variation frontal\/parietal additional ossification site occurred in fetuses from mid\u2010 and high\u2010dose groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The majority of transplacental migration of antibody occurred in concert with rapid maternal serum clearance before parturition. The no\u2010observed effect level for teratogenicity of 5 mg\/kg was associated with GD 15 maternal serum concentrations 3\u201311\u2009times lower than clinical exposure of olaratumab, suggesting that olaratumab may cause fetal harm when administered to pregnant women.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1403","type":"journal-article","created":{"date-parts":[[2018,10,27]],"date-time":"2018-10-27T10:29:29Z","timestamp":1540636169000},"page":"1358-1371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["PDGFR\u03b1 monoclonal antibody: Assessment of embryo\u2010fetal toxicity and time\u2010dependent placental transfer of a murine surrogate antibody of olaratumab in mice"],"prefix":"10.1002","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5841-5063","authenticated-orcid":false,"given":"Debra","family":"Luffer\u2010Atlas","sequence":"first","affiliation":[{"name":"Lilly Research Laboratories, Corporate Center Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijayapal R.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Corporate Center Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim G.","family":"Hilbish","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Corporate Center Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Curtis E.","family":"Grace","sequence":"additional","affiliation":[{"name":"Covance Laboratories  Greenfield Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0139-9693","authenticated-orcid":false,"given":"William J","family":"Breslin","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Corporate Center Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1653708"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.10067"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.21089"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1052503"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1191\/096032700678815783"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01811.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581809337262"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.1.5.9676"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2004.06.007"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(16)36111-7"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/10520292609115636"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2011.653487"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00441-08"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.149.5.1019"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.11.4013-4025.2003"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-11-97"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.4.1283"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00721"},{"key":"e_1_2_8_20_1","unstructured":"International Conference on Harmonization (ICH).2005. 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