Regulatory approval and a first‐in‐human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants

Although plant biotechnology has been widely investigated for the production of clinical‐grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma‐Planta project, the HIV‐neutralizing human...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Plant biotechnology journal Jg. 13; H. 8; S. 1106 - 1120
Hauptverfasser:	Ma, Julian K‐C, Drossard, Jürgen, Lewis, David, Altmann, Friedrich, Boyle, Julia, Christou, Paul, Cole, Tom, Dale, Philip, van Dolleweerd, Craig J, Isitt, Valerie, Katinger, Dietmar, Lobedan, Martin, Mertens, Hubert, Paul, Mathew J, Rademacher, Thomas, Sack, Markus, Hundleby, Penelope A. C, Stiegler, Gabriela, Stoger, Eva, Twyman, Richard M, Vcelar, Brigitta, Fischer, Rainer
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	England Blackwell Pub 01.10.2015 John Wiley & Sons, Inc
Schlagworte:	Acquired immune deficiency syndrome AIDS Animals Antibodies Antibodies, Monoclonal - biosynthesis Antibodies, Monoclonal - therapeutic use Application programming interface biopharmaceuticals Biotechnology Broadly Neutralizing Antibodies Cell culture Clinical trials Disease transmission Drug Approval Ebola virus ethics Female females Germany Glycomics good manufacturing practice good manufacturing practices guanosine monophosphate Guidelines HIV HIV Antibodies Human immunodeficiency virus human trial Humans Immune system Infections ingredients loci Manufacturing Medical research Molecular Sequence Data Monoclonal antibodies monoclonal antibody Nicotiana - genetics Nicotiana tabacum Pharmaceuticals phase I Phenotype plantibodies Plants (organisms) Plants, Genetically Modified Protein Stability Proteins Proteomics Rabbits Regulators Regulatory approval Seed banks Seeds Social Control, Formal standard operating procedures Tobacco Transformation, Genetic Transgenes Transgenic Transgenic plants Trends United Kingdom United Kingdom Germany United States > US transgenic plants phase I tobacco human trial monoclonal antibody good manufacturing practice
ISSN:	1467-7644, 1467-7652
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Abstract	Although plant biotechnology has been widely investigated for the production of clinical‐grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma‐Planta project, the HIV‐neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant‐derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant‐derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first‐in‐human, double‐blind, placebo‐controlled, randomized, dose‐escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant‐derived pharmaceutical proteins.
AbstractList	Although plant biotechnology has been widely investigated for the production of clinical-grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma-Planta project, the HIV-neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant-derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant-derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first-in-human, double-blind, placebo-controlled, randomized, dose-escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant-derived pharmaceutical proteins. Although plant biotechnology has been widely investigated for the production of clinical‐grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma‐Planta project, the HIV‐neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco ( Nicotiana tabacum ). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant‐derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant‐derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first‐in‐human, double‐blind, placebo‐controlled, randomized, dose‐escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant‐derived pharmaceutical proteins. Summary Although plant biotechnology has been widely investigated for the production of clinical‐grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma‐Planta project, the HIV‐neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant‐derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant‐derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first‐in‐human, double‐blind, placebo‐controlled, randomized, dose‐escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant‐derived pharmaceutical proteins.
Author	Katinger, Dietmar Paul, Mathew J Drossard, Jürgen Mertens, Hubert Fischer, Rainer Ma, Julian K‐C Rademacher, Thomas Vcelar, Brigitta Dale, Philip Isitt, Valerie Lobedan, Martin Hundleby, Penelope A. C Stiegler, Gabriela Lewis, David Christou, Paul Twyman, Richard M Cole, Tom Boyle, Julia Sack, Markus Altmann, Friedrich van Dolleweerd, Craig J Stoger, Eva
Author_xml	– sequence: 1 fullname: Ma, Julian K‐C – sequence: 2 fullname: Drossard, Jürgen – sequence: 3 fullname: Lewis, David – sequence: 4 fullname: Altmann, Friedrich – sequence: 5 fullname: Boyle, Julia – sequence: 6 fullname: Christou, Paul – sequence: 7 fullname: Cole, Tom – sequence: 8 fullname: Dale, Philip – sequence: 9 fullname: van Dolleweerd, Craig J – sequence: 10 fullname: Isitt, Valerie – sequence: 11 fullname: Katinger, Dietmar – sequence: 12 fullname: Lobedan, Martin – sequence: 13 fullname: Mertens, Hubert – sequence: 14 fullname: Paul, Mathew J – sequence: 15 fullname: Rademacher, Thomas – sequence: 16 fullname: Sack, Markus – sequence: 17 fullname: Hundleby, Penelope A. C – sequence: 18 fullname: Stiegler, Gabriela – sequence: 19 fullname: Stoger, Eva – sequence: 20 fullname: Twyman, Richard M – sequence: 21 fullname: Vcelar, Brigitta – sequence: 22 fullname: Fischer, Rainer
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/26147010$$D View this record in MEDLINE/PubMed
BookMark	eNqNks1u1DAUhSNURH9gwQuAJTZlMa2v49jJEqoCI1UCAV1b_svUVWKHOAHNDvEEPCNPwqUzw6ICaWzp-i6-c3Tke4-Lg5iiL4qnQM8Az_lgwhkwDuJBcQRcyIUUFTv423N-WBznfEspA1GJR8UhE8AlBXpU_PjoV3OnpzSuiR6GMX3VHdHREU3aMObp1_efIWK5mXsdyXCjsydLYrsQg0VyGgPW1CLep5hsl-KdfgomuTVBPzdb70iIiOqYVx51ZEpGW5vI0CGZHxcPW91l_2T7nhTXby4_X7xbXL1_u7x4dbWwgkux4E0tma6dN86UjWs9Mw13hrEKTOu4qI11TDDtpMdGct-K1oIXDa-8Nm1TnhSnG19M9WX2eVJ9yNZ3GMKnOSuoaQmcMdgDlVWJtwK6B4qOUkK1jytUQkDFGaIv7qG3aR7xb7MqqZACo9aA1LMtNZveOzWModfjWu3Gi8D5BrBjynn0rbJh0lNIEacROgVU_VkghQuk7hYIFS_vKXam_2K37t9C59f_B9WH18ud4vlG0eqk9GoMWV1_YhQEpYAjY2X5G7ws364
CitedBy_id	crossref_primary_10_1371_journal_pmed_1003495 crossref_primary_10_1111_pbi_12855 crossref_primary_10_1038_s41598_019_51656_1 crossref_primary_10_1038_s41598_023_39106_5 crossref_primary_10_1016_j_jplph_2020_153359 crossref_primary_10_1016_j_plantsci_2023_111797 crossref_primary_10_1016_j_biotechadv_2024_108403 crossref_primary_10_1186_s12864_022_08547_z crossref_primary_10_1134_S102144371705017X crossref_primary_10_1016_j_biotechadv_2017_03_011 crossref_primary_10_3390_vaccines8020189 crossref_primary_10_1111_pbi_12580 crossref_primary_10_1146_annurev_arplant_043015_111812 crossref_primary_10_1186_s12864_017_3791_6 crossref_primary_10_1002_advs_202506272 crossref_primary_10_1016_j_heliyon_2023_e17148 crossref_primary_10_3389_fpls_2022_1043478 crossref_primary_10_1007_s00299_015_1911_9 crossref_primary_10_1016_j_jbiosc_2024_01_007 crossref_primary_10_1007_s12033_021_00360_5 crossref_primary_10_1016_j_copbio_2019_11_004 crossref_primary_10_1111_pbi_12743 crossref_primary_10_1016_j_pep_2018_07_012 crossref_primary_10_3389_fpls_2016_00018 crossref_primary_10_1371_journal_pone_0193339 crossref_primary_10_1080_13102818_2018_1451780 crossref_primary_10_1186_s40538_024_00592_y crossref_primary_10_3390_plants12010038 crossref_primary_10_1080_21655979_2023_2244235 crossref_primary_10_3389_fbioe_2023_1238917 crossref_primary_10_3390_plants9070842 crossref_primary_10_1586_14760584_2016_1155987 crossref_primary_10_3389_fpls_2018_01893 crossref_primary_10_3390_pathogens10081051 crossref_primary_10_1111_pbi_12746 crossref_primary_10_2174_0929867325666171212093257 crossref_primary_10_1016_j_biotechadv_2020_107683 crossref_primary_10_2174_0929867324666170718114724 crossref_primary_10_3389_fpls_2020_00791 crossref_primary_10_1016_j_coviro_2017_07_019 crossref_primary_10_1134_S1021443724607766 crossref_primary_10_1016_j_biotechadv_2020_107681 crossref_primary_10_1186_s13015_023_00228_0 crossref_primary_10_3390_ijms21062140 crossref_primary_10_1080_21645515_2021_1965423 crossref_primary_10_1002_biot_201900308 crossref_primary_10_1016_j_biotechadv_2023_108197 crossref_primary_10_1080_14760584_2017_1232167 crossref_primary_10_1096_fj_15_283226 crossref_primary_10_1111_pbi_13207 crossref_primary_10_1186_s12864_020_07355_7 crossref_primary_10_1007_s11816_025_00993_x crossref_primary_10_1111_pbi_12478 crossref_primary_10_1016_j_copbio_2020_01_004 crossref_primary_10_1002_bit_27076 crossref_primary_10_3390_biology12040601 crossref_primary_10_1080_19490976_2020_1859813 crossref_primary_10_3390_genes14061150 crossref_primary_10_1016_j_chroma_2018_08_014 crossref_primary_10_3390_life13030617 crossref_primary_10_3389_fimmu_2020_576012 crossref_primary_10_3390_vaccines9070761 crossref_primary_10_3389_fbioe_2020_00393 crossref_primary_10_1002_pep2_24290 crossref_primary_10_3389_fpls_2019_01245 crossref_primary_10_3390_ijms241210045 crossref_primary_10_1007_s12033_019_00233_y crossref_primary_10_1042_BCJ20200610 crossref_primary_10_1016_j_tibtech_2016_12_002 crossref_primary_10_1111_pbi_12928 crossref_primary_10_1016_j_biotechadv_2021_107768 crossref_primary_10_1016_j_rsci_2019_04_001 crossref_primary_10_1016_j_fbp_2021_04_013 crossref_primary_10_3389_fbioe_2019_00472 crossref_primary_10_3390_pathogens9020148 crossref_primary_10_1002_bit_26951 crossref_primary_10_1016_j_tibtech_2018_05_010 crossref_primary_10_1111_pbi_14429 crossref_primary_10_3390_plants8120560 crossref_primary_10_1080_07388551_2021_1888070 crossref_primary_10_1111_pbi_14034 crossref_primary_10_1007_s12257_020_0374_1 crossref_primary_10_1016_j_coviro_2021_12_005 crossref_primary_10_1002_wnan_1462 crossref_primary_10_1126_science_aaf6638 crossref_primary_10_1016_j_biotechadv_2018_02_002 crossref_primary_10_3389_fpls_2023_1276148 crossref_primary_10_3389_fceng_2021_737010 crossref_primary_10_1093_infdis_jiaa377 crossref_primary_10_1016_j_biotechadv_2020_107519 crossref_primary_10_1016_j_biotechadv_2022_107913 crossref_primary_10_1371_journal_pone_0274737 crossref_primary_10_1371_journal_pone_0167086 crossref_primary_10_1016_j_biotechadv_2019_06_012 crossref_primary_10_1002_biot_201900113 crossref_primary_10_3390_ijms26157046 crossref_primary_10_1111_pbi_13110 crossref_primary_10_1002_bit_27093 crossref_primary_10_1146_annurev_anchem_071015_041706 crossref_primary_10_1002_biot_202000340 crossref_primary_10_1007_s11816_024_00956_8 crossref_primary_10_1073_pnas_1806022115 crossref_primary_10_1111_pbi_13194 crossref_primary_10_3389_fmicb_2024_1383976 crossref_primary_10_1016_j_heliyon_2024_e37634 crossref_primary_10_1111_bcp_13041 crossref_primary_10_3390_horticulturae9121262 crossref_primary_10_1111_pbi_12541 crossref_primary_10_1007_s10529_019_02651_z crossref_primary_10_3390_vaccines10050772 crossref_primary_10_3390_vaccines9111365 crossref_primary_10_3390_molecules26134032 crossref_primary_10_1038_s44222_023_00044_6 crossref_primary_10_1128_JVI_00796_21 crossref_primary_10_1007_s11248_021_00236_z crossref_primary_10_1016_j_jbiotec_2024_05_003 crossref_primary_10_3389_fbioe_2022_838365 crossref_primary_10_3389_fpls_2021_736299 crossref_primary_10_1016_j_jbiotec_2016_12_017 crossref_primary_10_1016_j_tplants_2020_04_009 crossref_primary_10_1073_pnas_2107832118 crossref_primary_10_1016_j_freeradbiomed_2020_11_030 crossref_primary_10_1038_s41587_023_01812_w crossref_primary_10_1134_S0006297916100102 crossref_primary_10_1126_science_abf5375 crossref_primary_10_3389_fpls_2022_1012583 crossref_primary_10_1016_j_jpba_2019_112920 crossref_primary_10_1016_j_jbiotec_2024_04_001 crossref_primary_10_1016_j_jbiotec_2025_06_014 crossref_primary_10_3389_fpls_2023_1149455 crossref_primary_10_3390_agriculture11121195 crossref_primary_10_3390_agriculture5040901 crossref_primary_10_3390_ijms242417575 crossref_primary_10_1016_j_tibtech_2023_03_007 crossref_primary_10_1111_pbi_13092 crossref_primary_10_3390_plants10020352 crossref_primary_10_1186_s12977_021_00560_6 crossref_primary_10_1016_j_jpba_2022_114796 crossref_primary_10_1186_s12870_020_02412_5 crossref_primary_10_3389_fmolb_2021_666756 crossref_primary_10_1126_scitranslmed_abd5219 crossref_primary_10_1128_cmr_00152_22 crossref_primary_10_1111_pbi_14460 crossref_primary_10_17221_8_2021_CJGPB crossref_primary_10_12688_f1000research_8010_1 crossref_primary_10_3389_fpls_2016_00297 crossref_primary_10_1111_pbi_70231 crossref_primary_10_1111_pbi_70350 crossref_primary_10_1111_pbi_13657 crossref_primary_10_1111_pbi_13658 crossref_primary_10_3389_fpls_2020_594019 crossref_primary_10_3389_fpls_2023_1126470 crossref_primary_10_1007_s12033_018_0075_6 crossref_primary_10_3389_fpls_2020_589995 crossref_primary_10_1186_s12977_018_0455_9 crossref_primary_10_1016_j_biomaterials_2023_122312 crossref_primary_10_1097_QAD_0000000000001521 crossref_primary_10_3389_fpls_2021_682953 crossref_primary_10_3389_fpls_2022_1003065 crossref_primary_10_1016_j_chroma_2021_462379 crossref_primary_10_1186_s12896_020_00607_0 crossref_primary_10_3390_v15051156
Cites_doi	10.1093/jac/dkh428 10.1038/nature10373 10.1016/j.copbio.2014.12.008 10.1016/j.biotechadv.2011.08.007 10.1371/journal.pone.0013976 10.1111/pbi.12127 10.1038/342076a0 10.1073/pnas.0708841104 10.1038/nature13777 10.1038/sj.embor.7400470 10.1128/AAC.50.5.1773-1779.2006 10.1128/JVI.78.24.14039-14042.2004 10.1136/bmj.g5488 10.1046/j.1467-7652.2003.00041.x 10.1038/nrg1177 10.1159/000070184 10.1371/journal.pone.0058724 10.1038/72309 10.1038/nrmicro729 10.1126/science.227.4691.1229 10.1073/pnas.1213709109 10.1111/j.1467-7652.2007.00306.x 10.2174/138161210790232202 10.1517/14728214.10.1.185 10.1038/72318 10.1016/j.virol.2008.02.007 10.1002/pmic.200700968 10.1016/j.celrep.2013.11.015 10.1097/00002030-200201250-00012 10.1111/j.1467-7652.2010.00540.x 10.1016/j.tplants.2005.10.009 10.1016/S0140-6736(04)15876-5 10.1111/j.1467-7652.2008.00330.x 10.1128/JVI.78.23.13232-13252.2004 10.2174/1381612811319310003 10.1128/JVI.01564-08 10.3109/10731190009118582 10.1111/j.1467-7652.2009.00452.x 10.1073/pnas.97.22.11984 10.1038/nm833 10.1111/pbi.12360 10.1146/annurev-arplant-050213-035850 10.1371/journal.pone.0025165
ContentType	Journal Article
Copyright	2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd. 2015. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Copyright_xml	– notice: 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd – notice: 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd. – notice: 2015. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
DBID	FBQ AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QO 8FD FR3 P64 7X8 7U5 F28 L7M 7S9 L.6
DOI	10.1111/pbi.12416
DatabaseName	AGRIS CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Biotechnology Research Abstracts Technology Research Database Engineering Research Database Biotechnology and BioEngineering Abstracts MEDLINE - Academic Solid State and Superconductivity Abstracts ANTE: Abstracts in New Technology & Engineering Advanced Technologies Database with Aerospace AGRICOLA AGRICOLA - Academic
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Engineering Research Database Biotechnology Research Abstracts Technology Research Database Biotechnology and BioEngineering Abstracts MEDLINE - Academic Solid State and Superconductivity Abstracts Advanced Technologies Database with Aerospace ANTE: Abstracts in New Technology & Engineering AGRICOLA AGRICOLA - Academic
DatabaseTitleList	Solid State and Superconductivity Abstracts Engineering Research Database MEDLINE - Academic CrossRef Engineering Research Database AGRICOLA MEDLINE
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Agriculture
EISSN	1467-7652
EndPage	1120
ExternalDocumentID	26147010 10_1111_pbi_12416 PBI12416 US201600127423
Genre	reviewArticle Clinical Trial, Phase I Randomized Controlled Trial Research Support, Non-U.S. Gov't Journal Article
GeographicLocations	United Kingdom Germany United States--US
GeographicLocations_xml	– name: United Kingdom – name: Germany – name: United States--US
GrantInformation_xml	– fundername: COST Action Molecular Farming funderid: FA0804 – fundername: Wellcome Trust funderid: 37872 – fundername: ERC advanced grant Future‐Pharma funderid: 269110 – fundername: CoMoFarm funderid: 227420 – fundername: Fraunhofer Gesellschaft – fundername: Grand Challenges in Global Health – fundername: European Union for the Pharma‐Planta project funderid: LSHB‐CT‐2003‐503565
GroupedDBID	--- .3N .GA .Y3 05W 0R~ 10A 123 1OC 24P 29O 31~ 33P 4.4 50Y 50Z 51W 51X 52M 52N 52O 52P 52S 52T 52W 52X 53G 5HH 5LA 5VS 66C 702 7PT 8-0 8-1 8-3 8-4 8-5 8FE 8FG 8FH 8UM 930 A03 A8Z AAEVG AAHHS AAONW AAZKR ABCQN ABDBF ABEML ABIJN ABJCF ABPTK ABPVW ACBWZ ACCFJ ACIWK ACPRK ACSCC ACXME ACXQS ADBBV ADIZJ ADKYN ADZMN AEEZP AEIMD AENEX AEQDE AEUQT AFBPY AFEBI AFKRA AFRAH AFZJQ AIWBW AJBDE ALAGY ALMA_UNASSIGNED_HOLDINGS AMBMR ASPBG ATUGU AVUZU AVWKF AZBYB AZFZN BAFTC BBNVY BCNDV BDRZF BENPR BFHJK BGLVJ BHPHI BNHUX BROTX BRXPI BY8 CAG CCPQU COF CS3 D-E D-F DPXWK DR2 DU5 EAD EAP EBD EBS ECGQY EDH EJD EMK EMOBN EST ESTFP ESX F00 F01 F04 F5P FBQ FEDTE G-S G.N GODZA GROUPED_DOAJ H.T H.X HCIFZ HF~ HOLLA HVGLF HZ~ IAO IEP IGS IHE IX1 J0M KQ8 L6V LC2 LC3 LH4 LK8 LP6 LP7 LW6 M7P M7S MK4 ML0 N04 N05 N9A NF~ O66 O9- OK1 P2P P2X P4D PIMPY PROAC PTHSS Q.N Q11 QB0 QM4 QO4 R.K ROL RX1 SUPJJ SV3 TUS UB1 W8V W99 WIH WIN WQJ WRC XG1 ~IA ~KM ~WT AAHBH AAMMB AANHP ACCMX ACRPL ACUHS ACYXJ ADNMO AEFGJ AEUYN AGQPQ AGXDD AIDQK AIDYY ALUQN ITC OIG PHGZM PHGZT PQGLB RPM AAYXX AFFHD BANNL CITATION O8X CGR CUY CVF ECM EIF NPM 7QO 8FD FR3 P64 7X8 7U5 F28 L7M 7S9 L.6
ID	FETCH-LOGICAL-c6476-49872a8debdb39dfe2b94db2251bfd468bcd262ad7ecd274ef6fc1e6945eabf93
IEDL.DBID	24P
ISICitedReferencesCount	184
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000364584800011&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	1467-7644
IngestDate	Fri Sep 05 17:25:21 EDT 2025 Mon Sep 08 03:49:54 EDT 2025 Tue Oct 07 09:50:03 EDT 2025 Mon Sep 08 03:58:46 EDT 2025 Wed Aug 13 03:22:25 EDT 2025 Mon Jul 21 05:45:59 EDT 2025 Sat Nov 29 03:52:01 EST 2025 Tue Nov 18 21:05:26 EST 2025 Wed Aug 20 07:24:14 EDT 2025 Wed Dec 27 19:25:52 EST 2023
IsDoiOpenAccess	false
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	8
Keywords	transgenic plants phase I tobacco human trial monoclonal antibody good manufacturing practice
Language	English
License	2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c6476-49872a8debdb39dfe2b94db2251bfd468bcd262ad7ecd274ef6fc1e6945eabf93
Notes	http://dx.doi.org/10.1111/pbi.12416 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3
OpenAccessLink	https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/pbi.12416
PMID	26147010
PQID	3067680381
PQPubID	1096352
PageCount	15
ParticipantIDs	proquest_miscellaneous_1803142219 proquest_miscellaneous_1753535510 proquest_miscellaneous_1722177159 proquest_miscellaneous_1715661542 proquest_journals_3067680381 pubmed_primary_26147010 crossref_citationtrail_10_1111_pbi_12416 crossref_primary_10_1111_pbi_12416 wiley_primary_10_1111_pbi_12416_PBI12416 fao_agris_US201600127423
PublicationCentury	2000
PublicationDate	October 2015
PublicationDateYYYYMMDD	2015-10-01
PublicationDate_xml	– month: 10 year: 2015 text: October 2015
PublicationDecade	2010
PublicationPlace	England
PublicationPlace_xml	– name: England – name: Southampton
PublicationTitle	Plant biotechnology journal
PublicationTitleAlternate	Plant Biotechnol J
PublicationYear	2015
Publisher	Blackwell Pub John Wiley & Sons, Inc
Publisher_xml	– name: Blackwell Pub – name: John Wiley & Sons, Inc
References	2002; 16 2014; 514 2004; 363 2011; 477 2010; 16 2006; 50 2000; 28 2000; 6 2009; 83 2015; 32 2005b; 10 2008; 8 2008; 105 1998; 81 1985; 227 2008; 6 2013; 8 2011; 6 2013; 5 2005; 23 2012; 30 2012; 109 2003; 55 2014; 65 2011; 9 2004; 54 2014; 349 2013; 19 2013; 11 2004; 78 2000; 97 1989; 342 2003; 9 2009; 286 2003; 4 2005; 10 2009; 7 2005a; 6 1982 2015 2003; 1 2008; 375 2010; 5 e_1_2_9_30_1 e_1_2_9_31_1 Worrall D. (e_1_2_9_46_1) 1998; 81 e_1_2_9_11_1 e_1_2_9_34_1 e_1_2_9_10_1 e_1_2_9_35_1 e_1_2_9_13_1 e_1_2_9_32_1 e_1_2_9_12_1 e_1_2_9_33_1 EFSA (e_1_2_9_8_1) 2009; 286 e_1_2_9_15_1 e_1_2_9_38_1 e_1_2_9_14_1 e_1_2_9_39_1 e_1_2_9_17_1 e_1_2_9_36_1 e_1_2_9_16_1 e_1_2_9_37_1 e_1_2_9_19_1 e_1_2_9_18_1 e_1_2_9_41_1 e_1_2_9_42_1 e_1_2_9_20_1 e_1_2_9_40_1 e_1_2_9_22_1 e_1_2_9_45_1 e_1_2_9_24_1 e_1_2_9_43_1 e_1_2_9_23_1 e_1_2_9_44_1 e_1_2_9_7_1 e_1_2_9_6_1 e_1_2_9_5_1 e_1_2_9_4_1 e_1_2_9_3_1 e_1_2_9_2_1 Maniatis T. (e_1_2_9_21_1) 1982 e_1_2_9_9_1 e_1_2_9_26_1 e_1_2_9_25_1 e_1_2_9_28_1 e_1_2_9_47_1 e_1_2_9_27_1 e_1_2_9_29_1
References_xml	– volume: 286 start-page: 31 year: 2009 article-title: Potential risks for public health due to the presence of nicotine in wild mushrooms publication-title: EFSA J. – volume: 10 start-page: 580 year: 2005b end-page: 585 article-title: Plant‐derived pharmaceuticals–the road forward publication-title: Trends Plant Sci. – volume: 19 start-page: 5478 year: 2013 end-page: 5485 article-title: Target product selection—where can Molecular Pharming make the difference? publication-title: Curr. Pharm. Des. – year: 2015 article-title: Rice endosperm produces an underglycosylated and potent form of the HIV‐neutralizing monoclonal antibody 2G12 publication-title: Plant Biotechnol. J. – volume: 477 start-page: 466 year: 2011 end-page: 470 article-title: Broad neutralization coverage of HIV by multiple highly potent antibodies publication-title: Nature – volume: 105 start-page: 3727 year: 2008 end-page: 3732 article-title: Cost‐effective production of a vaginal protein microbicide to prevent HIV transmission publication-title: Proc. Natl Acad. Sci. USA – volume: 375 start-page: 315 year: 2008 end-page: 320 article-title: Recent advances in the characterization of HIV‐1 neutralization assays for standardized evaluation of the antibody response to infection and vaccination publication-title: Virology – volume: 4 start-page: 794 year: 2003 end-page: 805 article-title: The production of recombinant pharmaceutical proteins in plants publication-title: Nat. Rev. Genet. – volume: 6 start-page: 593 year: 2005a end-page: 599 article-title: Molecular farming for new drugs and vaccines. Current perspectives on the production of pharmaceuticals in transgenic plants publication-title: EMBO Rep. – volume: 32 start-page: 163 year: 2015 end-page: 170 article-title: The increasing value of plant‐made proteins publication-title: Curr. Opin. Biotechnol. – volume: 97 start-page: 11984 year: 2000 end-page: 11989 article-title: Biochemistry, mutagenesis, and oligomerization of DsRed, a red fluorescent protein from coral publication-title: Proc. Natl Acad. Sci. USA – volume: 78 start-page: 13232 year: 2004 end-page: 13252 article-title: Comprehensive cross‐clade neutralization analysis of a panel of anti‐human immunodeficiency virus type 1 monoclonal antibodies publication-title: J. Virol. – volume: 6 start-page: e25165 year: 2011 article-title: Phase I randomised clinical trial of an HIV‐1(CN54), clade C, trimeric envelope vaccine candidate delivered vaginally publication-title: PLoS ONE – volume: 11 start-page: 1029 year: 2013 end-page: 1033 article-title: Realising the value of plant molecular pharming to benefit the poor in developing countries and emerging economies publication-title: Plant Biotechnol. J. – volume: 7 start-page: 899 year: 2009 end-page: 913 article-title: Influence of elastin‐like peptide fusions on the quantity and quality of a tobacco‐derived human immunodeficiency virus‐neutralizing antibody publication-title: Plant Biotechnol. J. – volume: 30 start-page: 434 year: 2012 end-page: 439 article-title: GMP issues for recombinant plant‐derived pharmaceutical proteins publication-title: Biotechnol. Adv. – volume: 54 start-page: 915 year: 2004 end-page: 920 article-title: Passive immunization with the anti‐HIV‐1 human monoclonal antibody (hMAb) 4E10 and the hMAb combination 4E10/2F5/2G12 publication-title: J. Antimicrob. Chemother. – volume: 5 start-page: 1443 year: 2013 end-page: 1455 article-title: Structural basis for enhanced HIV‐1 neutralization by a dimeric immunoglobulin G form of the glycan‐recognizing antibody 2G12 publication-title: Cell Rep. – volume: 9 start-page: 179 year: 2011 end-page: 192 article-title: Production of monoclonal antibodies with a controlled N‐glycosylation pattern in seeds of Arabidopsis thaliana publication-title: Plant Biotechnol. J. – volume: 78 start-page: 14039 year: 2004 end-page: 14042 article-title: Neutralization profiles of newly transmitted human immunodeficiency virus type 1 by monoclonal antibodies 2G12, 2F5, and 4E10 publication-title: J. Virol. – volume: 16 start-page: 468 year: 2010 end-page: 485 article-title: Can microbicides turn the tide against HIV? publication-title: Curr. Pharm. Des. – volume: 8 start-page: e58724 year: 2013 article-title: Rapid high‐level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems publication-title: PLoS ONE – volume: 1 start-page: 25 year: 2003 end-page: 34 article-title: Inhibiting sexual transmission of HIV‐1 infection publication-title: Nat. Rev. Microbiol. – volume: 81 start-page: 425 year: 1998 end-page: 436 article-title: Southern analysis of transgenic tobacco plants publication-title: Methods Mol. Biol. – volume: 50 start-page: 1773 year: 2006 end-page: 1779 article-title: Long‐term multiple‐dose pharmacokinetics of human monoclonal antibodies (MAbs) against human immunodeficiency virus type 1 envelope gp120 (MAb 2G12) and gp41 (MAbs 4E10 and 2F5) publication-title: Antimicrob. Agents Chemother. – year: 1982 – volume: 8 start-page: 2858 year: 2008 end-page: 2871 article-title: Analysis of immunoglobulin glycosylation by LC‐ESI‐MS of glycopeptides and oligosaccharides publication-title: Proteomics – volume: 65 start-page: 743 year: 2014 end-page: 768 article-title: Plant molecular pharming for the treatment of chronic and infectious diseases publication-title: Annu. Rev. Plant Biol. – volume: 349 start-page: g5488 year: 2014 article-title: US signs contract with ZMapp maker to accelerate development of the Ebola drug publication-title: BMJ – volume: 10 start-page: 185 year: 2005 end-page: 218 article-title: Transgenic plants in the biopharmaceutical market publication-title: Expert Opin. Emerg. Drugs – volume: 109 start-page: 18030 year: 2012 end-page: 18035 article-title: Delayed treatment of Ebola virus infection with plant‐derived monoclonal antibodies provides protection in rhesus macaques publication-title: Proc. Natl Acad. Sci. USA – volume: 6 start-page: 189 year: 2008 end-page: 201 article-title: Recombinant antibody 2G12 produced in maize endosperm efficiently neutralizes HIV‐1 and contains predominantly single‐GlcNAc N‐glycans publication-title: Plant Biotechnol. J. – volume: 9 start-page: 343 year: 2003 end-page: 346 article-title: Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV‐1 gp120 publication-title: Nat. Med. – volume: 23 start-page: 559 year: 2005 end-page: 565 article-title: Biopharmaceutical production in plants: problems, solutions and opportunities publication-title: Trends Biotechnol. – volume: 342 start-page: 76 year: 1989 end-page: 78 article-title: Production of antibodies in transgenic plants publication-title: Nature – volume: 227 start-page: 1229 year: 1985 end-page: 1231 article-title: A simple and general‐method for transferring genes into plants publication-title: Science – volume: 28 start-page: 375 year: 2000 end-page: 383 article-title: Removal of parvovirus B19 from hemoglobin solution by nanofiltration publication-title: Artif. Cells Blood Substit. Immobil. Biotechnol. – volume: 16 start-page: 227 year: 2002 end-page: 233 article-title: A phase I trial with two human monoclonal antibodies (hMAb 2F5, 2G12) against HIV‐1 publication-title: AIDS – volume: 55 start-page: 110 year: 2003 end-page: 113 article-title: Surface area of the human vagina as measured from vinyl polysiloxane casts publication-title: Gynecol. Obstet. Invest. – volume: 6 start-page: 200 year: 2000 end-page: 206 article-title: Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian‐human immunodeficiency virus infection publication-title: Nat. Med. – volume: 514 start-page: 47 year: 2014 end-page: 53 article-title: Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp publication-title: Nature – volume: 363 start-page: 1002 year: 2004 end-page: 1003 article-title: Microbicides–aids to safer sex publication-title: Lancet – volume: 83 start-page: 98 year: 2009 end-page: 104 article-title: Design and expression of a dimeric form of human immunodeficiency virus type 1 antibody 2G12 with increased neutralization potency publication-title: J. Virol. – volume: 5 start-page: e13976 year: 2010 article-title: Rapid transient production in plants by replicating and non‐replicating vectors yields high quality functional anti‐HIV antibody publication-title: PLoS ONE – volume: 6 start-page: 392 year: 2008 end-page: 402 article-title: Generation of glyco‐engineered for the production of monoclonal antibodies with a homogeneous human‐like N‐glycan structure publication-title: Plant Biotechnol. J. – volume: 6 start-page: 207 year: 2000 end-page: 210 article-title: Protection of macaques against vaginal transmission of a pathogenic HIV‐1/SIV chimeric virus by passive infusion of neutralizing antibodies publication-title: Nat. Med. – ident: e_1_2_9_4_1 doi: 10.1093/jac/dkh428 – ident: e_1_2_9_44_1 doi: 10.1038/nature10373 – ident: e_1_2_9_34_1 doi: 10.1016/j.copbio.2014.12.008 – ident: e_1_2_9_9_1 doi: 10.1016/j.biotechadv.2011.08.007 – ident: e_1_2_9_35_1 doi: 10.1371/journal.pone.0013976 – ident: e_1_2_9_20_1 doi: 10.1111/pbi.12127 – ident: e_1_2_9_12_1 doi: 10.1038/342076a0 – ident: e_1_2_9_31_1 doi: 10.1073/pnas.0708841104 – volume: 286 start-page: 31 year: 2009 ident: e_1_2_9_8_1 article-title: Potential risks for public health due to the presence of nicotine in wild mushrooms publication-title: EFSA J. – ident: e_1_2_9_29_1 doi: 10.1038/nature13777 – ident: e_1_2_9_18_1 doi: 10.1038/sj.embor.7400470 – ident: e_1_2_9_14_1 doi: 10.1128/AAC.50.5.1773-1779.2006 – volume-title: Molecular Cloning: A Laboratory Manual year: 1982 ident: e_1_2_9_21_1 – ident: e_1_2_9_24_1 doi: 10.1128/JVI.78.24.14039-14042.2004 – ident: e_1_2_9_23_1 doi: 10.1136/bmj.g5488 – ident: e_1_2_9_11_1 doi: 10.1046/j.1467-7652.2003.00041.x – ident: e_1_2_9_17_1 doi: 10.1038/nrg1177 – ident: e_1_2_9_27_1 doi: 10.1159/000070184 – ident: e_1_2_9_33_1 doi: 10.1371/journal.pone.0058724 – ident: e_1_2_9_5_1 doi: 10.1038/72309 – ident: e_1_2_9_36_1 doi: 10.1038/nrmicro729 – ident: e_1_2_9_13_1 doi: 10.1126/science.227.4691.1229 – ident: e_1_2_9_25_1 doi: 10.1073/pnas.1213709109 – ident: e_1_2_9_30_1 doi: 10.1111/j.1467-7652.2007.00306.x – ident: e_1_2_9_32_1 doi: 10.2174/138161210790232202 – ident: e_1_2_9_41_1 doi: 10.1517/14728214.10.1.185 – volume: 81 start-page: 425 year: 1998 ident: e_1_2_9_46_1 article-title: Southern analysis of transgenic tobacco plants publication-title: Methods Mol. Biol. – ident: e_1_2_9_22_1 doi: 10.1038/72318 – ident: e_1_2_9_28_1 doi: 10.1016/j.virol.2008.02.007 – ident: e_1_2_9_38_1 doi: 10.1002/pmic.200700968 – ident: e_1_2_9_47_1 doi: 10.1016/j.celrep.2013.11.015 – ident: e_1_2_9_3_1 doi: 10.1097/00002030-200201250-00012 – ident: e_1_2_9_16_1 doi: 10.1111/j.1467-7652.2010.00540.x – ident: e_1_2_9_19_1 doi: 10.1016/j.tplants.2005.10.009 – ident: e_1_2_9_37_1 doi: 10.1016/S0140-6736(04)15876-5 – ident: e_1_2_9_40_1 doi: 10.1111/j.1467-7652.2008.00330.x – ident: e_1_2_9_7_1 doi: 10.1128/JVI.78.23.13232-13252.2004 – ident: e_1_2_9_26_1 doi: 10.2174/1381612811319310003 – ident: e_1_2_9_45_1 doi: 10.1128/JVI.01564-08 – ident: e_1_2_9_2_1 doi: 10.3109/10731190009118582 – ident: e_1_2_9_10_1 doi: 10.1111/j.1467-7652.2009.00452.x – ident: e_1_2_9_6_1 doi: 10.1073/pnas.97.22.11984 – ident: e_1_2_9_43_1 doi: 10.1038/nm833 – ident: e_1_2_9_42_1 doi: 10.1111/pbi.12360 – ident: e_1_2_9_39_1 doi: 10.1146/annurev-arplant-050213-035850 – ident: e_1_2_9_15_1 doi: 10.1371/journal.pone.0025165
SSID	ssj0021656
Score	2.5425992
Snippet	Although plant biotechnology has been widely investigated for the production of clinical‐grade monoclonal antibodies, no antibody products derived from... Summary Although plant biotechnology has been widely investigated for the production of clinical‐grade monoclonal antibodies, no antibody products derived from... Although plant biotechnology has been widely investigated for the production of clinical-grade monoclonal antibodies, no antibody products derived from...
SourceID	proquest pubmed crossref wiley fao
SourceType	Aggregation Database Index Database Enrichment Source Publisher
StartPage	1106
SubjectTerms	Acquired immune deficiency syndrome AIDS Animals Antibodies Antibodies, Monoclonal - biosynthesis Antibodies, Monoclonal - therapeutic use Application programming interface biopharmaceuticals Biotechnology Broadly Neutralizing Antibodies Cell culture Clinical trials Disease transmission Drug Approval Ebola virus ethics Female females Germany Glycomics good manufacturing practice good manufacturing practices guanosine monophosphate Guidelines HIV HIV Antibodies Human immunodeficiency virus human trial Humans Immune system Infections ingredients loci Manufacturing Medical research Molecular Sequence Data Monoclonal antibodies monoclonal antibody Nicotiana - genetics Nicotiana tabacum Pharmaceuticals phase I Phenotype plantibodies Plants (organisms) Plants, Genetically Modified Protein Stability Proteins Proteomics Rabbits Regulators Regulatory approval Seed banks Seeds Social Control, Formal standard operating procedures Tobacco Transformation, Genetic Transgenes Transgenic Transgenic plants Trends United Kingdom
Title	Regulatory approval and a first‐in‐human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants
URI	https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fpbi.12416 https://www.ncbi.nlm.nih.gov/pubmed/26147010 https://www.proquest.com/docview/3067680381 https://www.proquest.com/docview/1715661542 https://www.proquest.com/docview/1722177159 https://www.proquest.com/docview/1753535510 https://www.proquest.com/docview/1803142219
Volume	13
WOSCitedRecordID	wos000364584800011&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVWIB databaseName: Wiley Online Library Free Content customDbUrl: eissn: 1467-7652 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0021656 issn: 1467-7644 databaseCode: WIN dateStart: 20030101 isFulltext: true titleUrlDefault: https://onlinelibrary.wiley.com providerName: Wiley-Blackwell – providerCode: PRVWIB databaseName: Wiley Online Library Open Access customDbUrl: eissn: 1467-7652 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0021656 issn: 1467-7644 databaseCode: 24P dateStart: 20030101 isFulltext: true titleUrlDefault: https://authorservices.wiley.com/open-science/open-access/browse-journals.html providerName: Wiley-Blackwell
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1bi9QwFA67qw_64F13dJUoPuxLZZtmcsGnVVwckGFQF-ct5LoWhrZMZ4V9E3-Bv9Ff4kl6wYV1EKQQCj0J7cm5fU1yDkIvp5qbQnhAqizojBbaZ1pIlvFAHHXiCAxiqlrygc_nYrmUix30ejgL0-WHGH-4Rc1I9joquDbtH0remPIVOKec7aJreV6IWLeB0MWItmJame5oEc84eP0-rVDcxjN2veSMdoOur4ozL4etye-c3P6vN76DbvXhJj7u5OMu2vHVPXTz-Gzdp9zw99GPj105-np9gVOGcZA9rCuHNQ4lxIa_vv8sK2hSNT_cfAW3h2d4OFGJU9kPXAcgB4mu7SqG9tB_U5raXeAmZZT1DpcVkIJfBIEtLY5mxNoaN6u4D-cBOj159_nt-6yvzJBZRjnLqBScaOG8caaQLnhiJHUGbENugqNMGOsII9pxDzec-sCCzT2TdOq1CbJ4iPaquvL7CBspBAtOM8sI9d6AhQGQQ12RwJU1E3Q4TJGyfdryWD1jpQb4AmxVia0T9GIkbbpcHVcR7cM8Kw2MbtXpJxIz7MXldwgrJ-hgmHzVa3KrIqRiIq6nTtDz8THoYFxY0ZWvz1uV84iCIRgl22gIoD8glNtopgVcYCa30IhYcADGgnEedQI6fiygYcqPYu_DJId_54JavJmlm8f_TvoE3QBuTbudjAdob7M-90_RdfttU7brZ0n5oOVLAe2X2fw3boo0hQ
linkProvider	Wiley-Blackwell
linkToHtml	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1baxNBFD60VVAfvGtjq47iQ19Wmt3JzCz0pYqlwRiKtti3Ya66EHaXJBX6Jv4Cf2N_Sc_MXrBQgyCBsJBvls2Zc_t2Zs4BeDNSXGfCIVNlXiU0Uy5RImcJ96mlVuyiQ4xdSyZ8OhWnp_nRGux1Z2Ga-hD9C7dgGdFfBwMPL6T_sPJaF28xOg3ZOtygmGiExg1fx9OeboW6Ms3ZIp5wDPttXaGwj6cfeiUarXtVXZdoXs1bY-A5uPd_j3wf7rYJJ9lvNOQBrLnyIdzZ_zZvi264R_Drc9OQvpqfk1hjHLWPqNISRXyB2eHFz99FiV-xnx-pv2PgI2PSnakksfEHqTzCUacrMwvJPY5fFrqy56SONWWdJUWJUIyMqLKFIcGRGFORehZ24jyGk4MPx-8Pk7Y3Q2IY5SyhueCpEtZpq7PcepfqnFqN3mGovaVMaGNTlirLHV5w6jzzZuhYTkdOaZ9nT2CjrEq3CUTnQjBvFTMspc5p9DFIc6jNIr0yegA73RxJ0xYuD_0zZrIjMChWGcU6gNc9tG6qdVwH2sSJlgoFvZAnX9JQYy8swGNiOYDtbvZla8sLGUgVE2FFdQCv-p_RCsPSiipddbaQQx54MKaj6SpMivwPgfkqzCjDDzrKFRgRWg7gvfA-TxsN7f8s8mHKd8PonaiIf5eCPHo3jhfP_h36Em4dHn-ayMl4-nELbqPkRs2-xm3YWM7P3HO4aX4si8X8RbTES_ifNuY
linkToPdf	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1baxQxFA5tFdEH79qtVaP40JcpnUwmyYAv9bK4WJZFLfQt5KoDy8ywuxX6Jv6C_sb-kp5kLlioiyADw8CeDLsn5_Ztku8g9CZXXGfCAVJlXiU0Uy5RomAJ98RSKw4gIMauJUd8OhUnJ8VsA73tz8K0_BDDH27BM2K8Dg7uGuv_8PJGl_uQnVK2iW7QnKfBpgmdDXAr8Mq0Z4t4wiHtd7xCYR_PMPRKNtr0qr6u0Lxat8bEM773f1_5PrrbFZz4sLWQB2jDVQ_RncPvi450wz1Cv7-0DenrxRmOHONgfVhVFivsS6gOL36dlxXcYj8_3PyAxIcnuD9TiWPjD1x7EAebrs08FPcwflXq2p7hJnLKOovLCkQhM4LJlgaHQGJMjZt52InzGB2PP357_ynpejMkhlHOEloITpSwTludFdY7ogtqNUSHVHtLmdDGEkaU5Q4eOHWeeZM6VtDcKe2L7AnaqurKbSOsCyGYt4oZRqhzGmIMwBxqswivjB6hvX6OpOmIy0P_jLnsAQyoVUa1jtDrQbRp2TquE9qGiZYKFL2Ux19J4NgLC_BQWI7Qbj_7svPlpQygiomwojpCr4aPwQvD0oqqXH26lCkPOBjKUbJOhgD-A8FinUyewQWBco2MCC0H4F3wnqethQ4_FvAw5Qdh9F40xL9rQc7eTeLDzr-LvkS3Zh_G8mgy_fwM3QbF5e22xl20tVqcuufopvm5KpeLF9ERLwGXeDX9
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Regulatory+approval+and+a+first-in-human+phase+I+clinical+trial+of+a+monoclonal+antibody+produced+in+transgenic+tobacco+plants&rft.jtitle=Plant+biotechnology+journal&rft.au=Ma%2C+Julian+K-C&rft.au=Drossard%2C+J%C3%BCrgen&rft.au=Lewis%2C+David&rft.au=Altmann%2C+Friedrich&rft.date=2015-10-01&rft.eissn=1467-7652&rft.volume=13&rft.issue=8&rft.spage=1106&rft.epage=1120&rft_id=info:doi/10.1111%2Fpbi.12416&rft.externalDBID=NO_FULL_TEXT
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1467-7644&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1467-7644&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1467-7644&client=summon