title: Pre- and postnatal development in the cynomolgus monkey following administration of ABT-874, a human anti-IL-12/23p40 monoclonal antibody.
abstract: BACKGROUND
  ABT-874 is an anti-IL-12/23 monoclonal antibody that binds to the p40 subunit of human IL-12 and IL-23. As part of its preclinical safety assessment, studies were conducted to assess its potential effects on pre- and postnatal development in cynomolgus monkeys.
  
  
  METHODS
  In the embryo-fetal development studies, ABT-874 was administered once weekly subcutaneously to adult female cynomolgus monkeys at doses of 0, 5, 25, or 100 mg/kg during gestation days (GD) 20 to 48. Fetuses were examined for external, visceral, and skeletal development on GD 100 or 150. In the pre- and postnatal study, ABT-874 was administered once weekly subcutaneously to adult female cynomolgus monkeys at doses of 10, 50, or 200 mg/kg from GD 20 through postpartum day 182. Infants were examined from birth up to 9 months of age for morphological and functional development. Potential effects on the infant immune system were evaluated by immunophenotyping of peripheral blood lymphocytes and by T-dependent antibody response to KLH.
  
  
  RESULTS
  There was no ABT-874-related maternal toxicity or adverse effects on fetuses or infants. ABT-874 was present in maternal and fetal serum at GD 100 and 150, and in infant serum through day 63 postbirth. ABT-874 was also present at low levels in breast milk through postpartum day 175.
  
  
  CONCLUSIONS
  Exposure of cynomolgus monkey fetuses and infants to ABT-874 had no adverse effects on embryo-fetal or postnatal development.
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois 60064, USA. brian.enright@abbott.com
authors.forename: Brian P
authors.initials: BP
authors.lastname: Enright
authors.forename: Belen
authors.initials: B
authors.lastname: Tornesi
authors.forename: Gerhard F
authors.initials: GF
authors.lastname: Weinbauer
authors.forename: Guenter
authors.initials: G
authors.lastname: Blaich
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D000917:Antibody Formation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D006433:Hemocyanins / Q000494:pharmacology; D007107:Immune System / Q000187:drug effects; D007279:Injections, Subcutaneous; D007774:Lactation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008252:Macaca fascicularis / Q000502:physiology*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D018675:Toxicity Tests
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006433:Hemocyanins; C544528:briakinumab; C032808:keyhole-limpet hemocyanin