Pre- and Postnatal Development in the Cynomolgus Monkey Following Administration of ABT-874, a Human Anti-IL-12/23p40 Monoclonal Antibody
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...
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| Veröffentlicht in: | Birth defects research. Part B. Developmental and reproductive toxicology 2012-12, Vol.95 (6), p.431-443 |
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| container_title | Birth defects research. Part B. Developmental and reproductive toxicology |
| container_volume | 95 |
| creator | Enright, Brian P. Tornesi, Belen Weinbauer, Gerhard F. Blaich, Guenter |
| description | 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. |
| doi_str_mv | 10.1002/bdrb.21034 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1237090969</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1237090969</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3954-9994fa137302a410d0f9f2756d04eae11732e0dc3e1cbcd485fe6b956e581d8b3</originalsourceid><addsrcrecordid>eNp9kctu1DAUhiMEoqWw4QGQJTYIkdbXJF7OTOlFmkJBRbCznPikpHXswU4oeQTeGodpZ8GClY_k7_zn2F-WvST4kGBMj2oT6kNKMOOPsn0iOM1lycnjXc3YXvYsxpvEsrKsnmZ7lFFCS0H3s9-XAXKknUGXPg5OD9qiY_gJ1m96cAPqHBq-A1pNzvfeXo8RXXh3CxM68db6u85do4XpO9fFIeih8w75Fi2WV3lV8ndIo7Ox1w4t3NDl5-uc0CPKNhzPIb6x3qVp813tzfQ8e9JqG-HF_XmQfTl5f7U6y9cfT89Xi3XeMCl4LqXkrSasZJhqTrDBrWzTWwqDOWggpGQUsGkYkKZuDK9EC0UtRQGiIqaq2UH2Zpu7Cf7HCHFQfRcbsFY78GNUJH0SllgWMqGv_0Fv_BjS0jNVFJyKquCJerulmuBjDNCqTeh6HSZFsJoFqVmQ-isowa_uI8e6B7NDH4wkgGyBu87C9J8otTz-vHwIzbc9yQL82vXocKuKkpVCff1wqopCkG9MXKhP7A_mIadS</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1266425864</pqid></control><display><type>article</type><title>Pre- and Postnatal Development in the Cynomolgus Monkey Following Administration of ABT-874, a Human Anti-IL-12/23p40 Monoclonal Antibody</title><source>Wiley Online Library - AutoHoldings Journals</source><source>MEDLINE</source><creator>Enright, Brian P. ; Tornesi, Belen ; Weinbauer, Gerhard F. ; Blaich, Guenter</creator><creatorcontrib>Enright, Brian P. ; Tornesi, Belen ; Weinbauer, Gerhard F. ; Blaich, Guenter</creatorcontrib><description>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.</description><identifier>ISSN: 1542-9733</identifier><identifier>EISSN: 1542-9741</identifier><identifier>DOI: 10.1002/bdrb.21034</identifier><identifier>PMID: 23212752</identifier><identifier>CODEN: BDRPCU</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>ABT-874 ; Animals ; Animals, Newborn ; Antibodies, Monoclonal - toxicity ; Antibody Formation - drug effects ; Body Weight - drug effects ; cynomolgus monkey ; Dose-Response Relationship, Drug ; embryo ; Embryo, Mammalian - drug effects ; Embryonic Development - drug effects ; Female ; Fetal Development - drug effects ; fetus ; Fetuses ; Hemocyanins - pharmacology ; Immune System - drug effects ; Injections, Subcutaneous ; interleukin 12/23 ; Lactation - drug effects ; Lymphocytes - drug effects ; Macaca fascicularis - physiology ; Male ; Maternal Exposure - adverse effects ; Medical research ; Monoclonal antibodies ; Pregnancy ; Prenatal Exposure Delayed Effects - chemically induced ; Toxicity Tests</subject><ispartof>Birth defects research. Part B. Developmental and reproductive toxicology, 2012-12, Vol.95 (6), p.431-443</ispartof><rights>2012 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3954-9994fa137302a410d0f9f2756d04eae11732e0dc3e1cbcd485fe6b956e581d8b3</citedby><cites>FETCH-LOGICAL-c3954-9994fa137302a410d0f9f2756d04eae11732e0dc3e1cbcd485fe6b956e581d8b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fbdrb.21034$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fbdrb.21034$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23212752$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Enright, Brian P.</creatorcontrib><creatorcontrib>Tornesi, Belen</creatorcontrib><creatorcontrib>Weinbauer, Gerhard F.</creatorcontrib><creatorcontrib>Blaich, Guenter</creatorcontrib><title>Pre- and Postnatal Development in the Cynomolgus Monkey Following Administration of ABT-874, a Human Anti-IL-12/23p40 Monoclonal Antibody</title><title>Birth defects research. Part B. Developmental and reproductive toxicology</title><addtitle>Birth Defects Res B</addtitle><description>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.</description><subject>ABT-874</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Antibodies, Monoclonal - toxicity</subject><subject>Antibody Formation - drug effects</subject><subject>Body Weight - drug effects</subject><subject>cynomolgus monkey</subject><subject>Dose-Response Relationship, Drug</subject><subject>embryo</subject><subject>Embryo, Mammalian - drug effects</subject><subject>Embryonic Development - drug effects</subject><subject>Female</subject><subject>Fetal Development - drug effects</subject><subject>fetus</subject><subject>Fetuses</subject><subject>Hemocyanins - pharmacology</subject><subject>Immune System - drug effects</subject><subject>Injections, Subcutaneous</subject><subject>interleukin 12/23</subject><subject>Lactation - drug effects</subject><subject>Lymphocytes - drug effects</subject><subject>Macaca fascicularis - physiology</subject><subject>Male</subject><subject>Maternal Exposure - adverse effects</subject><subject>Medical research</subject><subject>Monoclonal antibodies</subject><subject>Pregnancy</subject><subject>Prenatal Exposure Delayed Effects - chemically induced</subject><subject>Toxicity Tests</subject><issn>1542-9733</issn><issn>1542-9741</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1DAUhiMEoqWw4QGQJTYIkdbXJF7OTOlFmkJBRbCznPikpHXswU4oeQTeGodpZ8GClY_k7_zn2F-WvST4kGBMj2oT6kNKMOOPsn0iOM1lycnjXc3YXvYsxpvEsrKsnmZ7lFFCS0H3s9-XAXKknUGXPg5OD9qiY_gJ1m96cAPqHBq-A1pNzvfeXo8RXXh3CxM68db6u85do4XpO9fFIeih8w75Fi2WV3lV8ndIo7Ox1w4t3NDl5-uc0CPKNhzPIb6x3qVp813tzfQ8e9JqG-HF_XmQfTl5f7U6y9cfT89Xi3XeMCl4LqXkrSasZJhqTrDBrWzTWwqDOWggpGQUsGkYkKZuDK9EC0UtRQGiIqaq2UH2Zpu7Cf7HCHFQfRcbsFY78GNUJH0SllgWMqGv_0Fv_BjS0jNVFJyKquCJerulmuBjDNCqTeh6HSZFsJoFqVmQ-isowa_uI8e6B7NDH4wkgGyBu87C9J8otTz-vHwIzbc9yQL82vXocKuKkpVCff1wqopCkG9MXKhP7A_mIadS</recordid><startdate>201212</startdate><enddate>201212</enddate><creator>Enright, Brian P.</creator><creator>Tornesi, Belen</creator><creator>Weinbauer, Gerhard F.</creator><creator>Blaich, Guenter</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201212</creationdate><title>Pre- and Postnatal Development in the Cynomolgus Monkey Following Administration of ABT-874, a Human Anti-IL-12/23p40 Monoclonal Antibody</title><author>Enright, Brian P. ; Tornesi, Belen ; Weinbauer, Gerhard F. ; Blaich, Guenter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3954-9994fa137302a410d0f9f2756d04eae11732e0dc3e1cbcd485fe6b956e581d8b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>ABT-874</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Antibodies, Monoclonal - toxicity</topic><topic>Antibody Formation - drug effects</topic><topic>Body Weight - drug effects</topic><topic>cynomolgus monkey</topic><topic>Dose-Response Relationship, Drug</topic><topic>embryo</topic><topic>Embryo, Mammalian - drug effects</topic><topic>Embryonic Development - drug effects</topic><topic>Female</topic><topic>Fetal Development - drug effects</topic><topic>fetus</topic><topic>Fetuses</topic><topic>Hemocyanins - pharmacology</topic><topic>Immune System - drug effects</topic><topic>Injections, Subcutaneous</topic><topic>interleukin 12/23</topic><topic>Lactation - drug effects</topic><topic>Lymphocytes - drug effects</topic><topic>Macaca fascicularis - physiology</topic><topic>Male</topic><topic>Maternal Exposure - adverse effects</topic><topic>Medical research</topic><topic>Monoclonal antibodies</topic><topic>Pregnancy</topic><topic>Prenatal Exposure Delayed Effects - chemically induced</topic><topic>Toxicity Tests</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Enright, Brian P.</creatorcontrib><creatorcontrib>Tornesi, Belen</creatorcontrib><creatorcontrib>Weinbauer, Gerhard F.</creatorcontrib><creatorcontrib>Blaich, Guenter</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Birth defects research. Part B. Developmental and reproductive toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Enright, Brian P.</au><au>Tornesi, Belen</au><au>Weinbauer, Gerhard F.</au><au>Blaich, Guenter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pre- and Postnatal Development in the Cynomolgus Monkey Following Administration of ABT-874, a Human Anti-IL-12/23p40 Monoclonal Antibody</atitle><jtitle>Birth defects research. Part B. Developmental and reproductive toxicology</jtitle><addtitle>Birth Defects Res B</addtitle><date>2012-12</date><risdate>2012</risdate><volume>95</volume><issue>6</issue><spage>431</spage><epage>443</epage><pages>431-443</pages><issn>1542-9733</issn><eissn>1542-9741</eissn><coden>BDRPCU</coden><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.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>23212752</pmid><doi>10.1002/bdrb.21034</doi><tpages>13</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1542-9733 |
| ispartof | Birth defects research. Part B. Developmental and reproductive toxicology, 2012-12, Vol.95 (6), p.431-443 |
| issn | 1542-9733 1542-9741 |
| language | eng |
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| source | Wiley Online Library - AutoHoldings Journals; MEDLINE |
| subjects | ABT-874 Animals Animals, Newborn Antibodies, Monoclonal - toxicity Antibody Formation - drug effects Body Weight - drug effects cynomolgus monkey Dose-Response Relationship, Drug embryo Embryo, Mammalian - drug effects Embryonic Development - drug effects Female Fetal Development - drug effects fetus Fetuses Hemocyanins - pharmacology Immune System - drug effects Injections, Subcutaneous interleukin 12/23 Lactation - drug effects Lymphocytes - drug effects Macaca fascicularis - physiology Male Maternal Exposure - adverse effects Medical research Monoclonal antibodies Pregnancy Prenatal Exposure Delayed Effects - chemically induced Toxicity Tests |
| title | Pre- and Postnatal Development in the Cynomolgus Monkey Following Administration of ABT-874, a Human Anti-IL-12/23p40 Monoclonal Antibody |
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