Predictive modelling and simulation for taming the chance and luck in biologics drug discovery

Three Pillars of Survival paradigm in the pharmaceutical drug discovery stipulates that a drug candidate is more likely to reach Phase III if it meets the following criteria: 1) it reaches the required tissue compartment, 2) engages the desired target, 3) triggers the desired downstream pharmacologi...
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Autor*in:	Armin Sepp [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	physiologically-based pharmacokinetics pbpk biologics therapeutic antibodies therapeutic proteins

Übergeordnetes Werk:	In: Proceedings of the Estonian Academy of Sciences - Estonian Academy Publishers, 2018, 72(2023), 4, Seite 371-381
Übergeordnetes Werk:	volume:72 ; year:2023 ; number:4 ; pages:371-381

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

Katalog-ID:	DOAJ094639698

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allfields	(DE-627)DOAJ094639698 (DE-599)DOAJ2439d3adbd0d480880ad7701cead604b DE-627 ger DE-627 rakwb eng Armin Sepp verfasserin aut Predictive modelling and simulation for taming the chance and luck in biologics drug discovery 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Three Pillars of Survival paradigm in the pharmaceutical drug discovery stipulates that a drug candidate is more likely to reach Phase III if it meets the following criteria: 1) it reaches the required tissue compartment, 2) engages the desired target, 3) triggers the desired downstream pharmacological effect. This paper describes the progress made along this track for biologics, in the first instance for monoclonal antibodies, their fragments and therapeutic proteins in general. CrossÂspecies/crossÂmodality physiologicallyÂbased pharmacokinetics (PBPK) framework aims to provide the first principle quantitative predictions for the first two of the declared Pillars. The approach is based on twoÂpore hypothesis of extravasation, further developed with PBPK in mind and parameterized for fractional tissue lymph flow rates using rodent data. The biologics PBPK framework is validated by accurately predicting the tissue distribution and elimination properties of normal and modified antibodies and their fragments in primate and human studies. physiologically-based pharmacokinetics pbpk biologics therapeutic antibodies therapeutic proteins Science Q In Proceedings of the Estonian Academy of Sciences Estonian Academy Publishers, 2018 72(2023), 4, Seite 371-381 (DE-627)578539314 (DE-600)2452178-4 17367530 nnns volume:72 year:2023 number:4 pages:371-381 https://doi.org/10.3176/proc.2023.4.02 kostenfrei https://doaj.org/article/2439d3adbd0d480880ad7701cead604b kostenfrei https://kirj.ee/wp-content/plugins/kirj/pub/proc-4-2023-371-381_20231024125333.pdf kostenfrei https://doaj.org/toc/1736-6046 Journal toc kostenfrei https://doaj.org/toc/1736-7530 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 72 2023 4 371-381
spelling	(DE-627)DOAJ094639698 (DE-599)DOAJ2439d3adbd0d480880ad7701cead604b DE-627 ger DE-627 rakwb eng Armin Sepp verfasserin aut Predictive modelling and simulation for taming the chance and luck in biologics drug discovery 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Three Pillars of Survival paradigm in the pharmaceutical drug discovery stipulates that a drug candidate is more likely to reach Phase III if it meets the following criteria: 1) it reaches the required tissue compartment, 2) engages the desired target, 3) triggers the desired downstream pharmacological effect. This paper describes the progress made along this track for biologics, in the first instance for monoclonal antibodies, their fragments and therapeutic proteins in general. CrossÂspecies/crossÂmodality physiologicallyÂbased pharmacokinetics (PBPK) framework aims to provide the first principle quantitative predictions for the first two of the declared Pillars. The approach is based on twoÂpore hypothesis of extravasation, further developed with PBPK in mind and parameterized for fractional tissue lymph flow rates using rodent data. The biologics PBPK framework is validated by accurately predicting the tissue distribution and elimination properties of normal and modified antibodies and their fragments in primate and human studies. physiologically-based pharmacokinetics pbpk biologics therapeutic antibodies therapeutic proteins Science Q In Proceedings of the Estonian Academy of Sciences Estonian Academy Publishers, 2018 72(2023), 4, Seite 371-381 (DE-627)578539314 (DE-600)2452178-4 17367530 nnns volume:72 year:2023 number:4 pages:371-381 https://doi.org/10.3176/proc.2023.4.02 kostenfrei https://doaj.org/article/2439d3adbd0d480880ad7701cead604b kostenfrei https://kirj.ee/wp-content/plugins/kirj/pub/proc-4-2023-371-381_20231024125333.pdf kostenfrei https://doaj.org/toc/1736-6046 Journal toc kostenfrei https://doaj.org/toc/1736-7530 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 72 2023 4 371-381
allfields_unstemmed	(DE-627)DOAJ094639698 (DE-599)DOAJ2439d3adbd0d480880ad7701cead604b DE-627 ger DE-627 rakwb eng Armin Sepp verfasserin aut Predictive modelling and simulation for taming the chance and luck in biologics drug discovery 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Three Pillars of Survival paradigm in the pharmaceutical drug discovery stipulates that a drug candidate is more likely to reach Phase III if it meets the following criteria: 1) it reaches the required tissue compartment, 2) engages the desired target, 3) triggers the desired downstream pharmacological effect. This paper describes the progress made along this track for biologics, in the first instance for monoclonal antibodies, their fragments and therapeutic proteins in general. CrossÂspecies/crossÂmodality physiologicallyÂbased pharmacokinetics (PBPK) framework aims to provide the first principle quantitative predictions for the first two of the declared Pillars. The approach is based on twoÂpore hypothesis of extravasation, further developed with PBPK in mind and parameterized for fractional tissue lymph flow rates using rodent data. The biologics PBPK framework is validated by accurately predicting the tissue distribution and elimination properties of normal and modified antibodies and their fragments in primate and human studies. physiologically-based pharmacokinetics pbpk biologics therapeutic antibodies therapeutic proteins Science Q In Proceedings of the Estonian Academy of Sciences Estonian Academy Publishers, 2018 72(2023), 4, Seite 371-381 (DE-627)578539314 (DE-600)2452178-4 17367530 nnns volume:72 year:2023 number:4 pages:371-381 https://doi.org/10.3176/proc.2023.4.02 kostenfrei https://doaj.org/article/2439d3adbd0d480880ad7701cead604b kostenfrei https://kirj.ee/wp-content/plugins/kirj/pub/proc-4-2023-371-381_20231024125333.pdf kostenfrei https://doaj.org/toc/1736-6046 Journal toc kostenfrei https://doaj.org/toc/1736-7530 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 72 2023 4 371-381
allfieldsGer	(DE-627)DOAJ094639698 (DE-599)DOAJ2439d3adbd0d480880ad7701cead604b DE-627 ger DE-627 rakwb eng Armin Sepp verfasserin aut Predictive modelling and simulation for taming the chance and luck in biologics drug discovery 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Three Pillars of Survival paradigm in the pharmaceutical drug discovery stipulates that a drug candidate is more likely to reach Phase III if it meets the following criteria: 1) it reaches the required tissue compartment, 2) engages the desired target, 3) triggers the desired downstream pharmacological effect. This paper describes the progress made along this track for biologics, in the first instance for monoclonal antibodies, their fragments and therapeutic proteins in general. CrossÂspecies/crossÂmodality physiologicallyÂbased pharmacokinetics (PBPK) framework aims to provide the first principle quantitative predictions for the first two of the declared Pillars. The approach is based on twoÂpore hypothesis of extravasation, further developed with PBPK in mind and parameterized for fractional tissue lymph flow rates using rodent data. The biologics PBPK framework is validated by accurately predicting the tissue distribution and elimination properties of normal and modified antibodies and their fragments in primate and human studies. physiologically-based pharmacokinetics pbpk biologics therapeutic antibodies therapeutic proteins Science Q In Proceedings of the Estonian Academy of Sciences Estonian Academy Publishers, 2018 72(2023), 4, Seite 371-381 (DE-627)578539314 (DE-600)2452178-4 17367530 nnns volume:72 year:2023 number:4 pages:371-381 https://doi.org/10.3176/proc.2023.4.02 kostenfrei https://doaj.org/article/2439d3adbd0d480880ad7701cead604b kostenfrei https://kirj.ee/wp-content/plugins/kirj/pub/proc-4-2023-371-381_20231024125333.pdf kostenfrei https://doaj.org/toc/1736-6046 Journal toc kostenfrei https://doaj.org/toc/1736-7530 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 72 2023 4 371-381
allfieldsSound	(DE-627)DOAJ094639698 (DE-599)DOAJ2439d3adbd0d480880ad7701cead604b DE-627 ger DE-627 rakwb eng Armin Sepp verfasserin aut Predictive modelling and simulation for taming the chance and luck in biologics drug discovery 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Three Pillars of Survival paradigm in the pharmaceutical drug discovery stipulates that a drug candidate is more likely to reach Phase III if it meets the following criteria: 1) it reaches the required tissue compartment, 2) engages the desired target, 3) triggers the desired downstream pharmacological effect. This paper describes the progress made along this track for biologics, in the first instance for monoclonal antibodies, their fragments and therapeutic proteins in general. CrossÂspecies/crossÂmodality physiologicallyÂbased pharmacokinetics (PBPK) framework aims to provide the first principle quantitative predictions for the first two of the declared Pillars. The approach is based on twoÂpore hypothesis of extravasation, further developed with PBPK in mind and parameterized for fractional tissue lymph flow rates using rodent data. The biologics PBPK framework is validated by accurately predicting the tissue distribution and elimination properties of normal and modified antibodies and their fragments in primate and human studies. physiologically-based pharmacokinetics pbpk biologics therapeutic antibodies therapeutic proteins Science Q In Proceedings of the Estonian Academy of Sciences Estonian Academy Publishers, 2018 72(2023), 4, Seite 371-381 (DE-627)578539314 (DE-600)2452178-4 17367530 nnns volume:72 year:2023 number:4 pages:371-381 https://doi.org/10.3176/proc.2023.4.02 kostenfrei https://doaj.org/article/2439d3adbd0d480880ad7701cead604b kostenfrei https://kirj.ee/wp-content/plugins/kirj/pub/proc-4-2023-371-381_20231024125333.pdf kostenfrei https://doaj.org/toc/1736-6046 Journal toc kostenfrei https://doaj.org/toc/1736-7530 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 72 2023 4 371-381
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author	Armin Sepp
spellingShingle	Armin Sepp misc physiologically-based pharmacokinetics misc pbpk misc biologics misc therapeutic antibodies misc therapeutic proteins misc Science misc Q Predictive modelling and simulation for taming the chance and luck in biologics drug discovery
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topic_title	Predictive modelling and simulation for taming the chance and luck in biologics drug discovery physiologically-based pharmacokinetics pbpk biologics therapeutic antibodies therapeutic proteins
topic	misc physiologically-based pharmacokinetics misc pbpk misc biologics misc therapeutic antibodies misc therapeutic proteins misc Science misc Q
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title	Predictive modelling and simulation for taming the chance and luck in biologics drug discovery
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title_full	Predictive modelling and simulation for taming the chance and luck in biologics drug discovery
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author-letter	Armin Sepp
title_sort	predictive modelling and simulation for taming the chance and luck in biologics drug discovery
title_auth	Predictive modelling and simulation for taming the chance and luck in biologics drug discovery
abstract	Three Pillars of Survival paradigm in the pharmaceutical drug discovery stipulates that a drug candidate is more likely to reach Phase III if it meets the following criteria: 1) it reaches the required tissue compartment, 2) engages the desired target, 3) triggers the desired downstream pharmacological effect. This paper describes the progress made along this track for biologics, in the first instance for monoclonal antibodies, their fragments and therapeutic proteins in general. CrossÂspecies/crossÂmodality physiologicallyÂbased pharmacokinetics (PBPK) framework aims to provide the first principle quantitative predictions for the first two of the declared Pillars. The approach is based on twoÂpore hypothesis of extravasation, further developed with PBPK in mind and parameterized for fractional tissue lymph flow rates using rodent data. The biologics PBPK framework is validated by accurately predicting the tissue distribution and elimination properties of normal and modified antibodies and their fragments in primate and human studies.
abstractGer	Three Pillars of Survival paradigm in the pharmaceutical drug discovery stipulates that a drug candidate is more likely to reach Phase III if it meets the following criteria: 1) it reaches the required tissue compartment, 2) engages the desired target, 3) triggers the desired downstream pharmacological effect. This paper describes the progress made along this track for biologics, in the first instance for monoclonal antibodies, their fragments and therapeutic proteins in general. CrossÂspecies/crossÂmodality physiologicallyÂbased pharmacokinetics (PBPK) framework aims to provide the first principle quantitative predictions for the first two of the declared Pillars. The approach is based on twoÂpore hypothesis of extravasation, further developed with PBPK in mind and parameterized for fractional tissue lymph flow rates using rodent data. The biologics PBPK framework is validated by accurately predicting the tissue distribution and elimination properties of normal and modified antibodies and their fragments in primate and human studies.
abstract_unstemmed	Three Pillars of Survival paradigm in the pharmaceutical drug discovery stipulates that a drug candidate is more likely to reach Phase III if it meets the following criteria: 1) it reaches the required tissue compartment, 2) engages the desired target, 3) triggers the desired downstream pharmacological effect. This paper describes the progress made along this track for biologics, in the first instance for monoclonal antibodies, their fragments and therapeutic proteins in general. CrossÂspecies/crossÂmodality physiologicallyÂbased pharmacokinetics (PBPK) framework aims to provide the first principle quantitative predictions for the first two of the declared Pillars. The approach is based on twoÂpore hypothesis of extravasation, further developed with PBPK in mind and parameterized for fractional tissue lymph flow rates using rodent data. The biologics PBPK framework is validated by accurately predicting the tissue distribution and elimination properties of normal and modified antibodies and their fragments in primate and human studies.
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title_short	Predictive modelling and simulation for taming the chance and luck in biologics drug discovery
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Predictive modelling and simulation for taming the chance and luck in biologics drug discovery

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