000429592 001__ 429592
000429592 005__ 20250729134857.0
000429592 0247_ $$2ISSN$$a0022-3549
000429592 0247_ $$2ISSN$$a1520-6017
000429592 0247_ $$2datacite_doi$$a10.3204/PUBDB-2019-05118
000429592 037__ $$aPUBDB-2019-05118
000429592 041__ $$aEnglish
000429592 082__ $$a610
000429592 1001_ $$00000-0001-5863-9569$$aSvilenov, Hristo L.$$b0
000429592 245__ $$aOrthogonal Techniques to Study the Effect of pH, Sucrose, and Arginine Salts on Monoclonal Antibody Physical Stability and Aggregation During Long-term Storage
000429592 260__ $$aAmsterdam$$bElsevier$$c2019
000429592 3367_ $$0PUB:(DE-HGF)25$$2PUB:(DE-HGF)$$aPreprint$$bpreprint$$mpreprint$$s1580492704_1873
000429592 3367_ $$2ORCID$$aWORKING_PAPER
000429592 3367_ $$028$$2EndNote$$aElectronic Article
000429592 3367_ $$2DRIVER$$apreprint
000429592 3367_ $$2BibTeX$$aARTICLE
000429592 3367_ $$2DataCite$$aOutput Types/Working Paper
000429592 500__ $$a© American Pharmacists Association®. Published by Elsevier Inc.
000429592 520__ $$aUnderstanding the effects of additives on therapeutic protein stability is of paramount importance for obtaining stable formulations. In this work, we apply several high- and medium-throughput methods to study the physical stability of a model monoclonal antibody at pH 5.0 and 6.5 in the presence of sucrose, arginine hydrochloride, and arginine glutamate. In low ionic strength buffer, the addition of salts reduces the antibody colloidal and thermal stability, attributed to screening of electrostatic interactions. The presence of glutamate ion in the arginine salt partially reduces the damaging effect of ionic strength increase. The addition of 280 mM sucrose shifts the thermal protein unfolding to a higher temperature. Arginine salts in the used concentration reduce the relative monomer yield after refolding from urea, whereas sucrose has a favorable effect on antibody refolding. In addition, we show 12-month long-term stability data and observe correlations between thermal protein stability, relative monomer yield after refolding, and monomer loss during storage. The monomer loss during storage is related to protein aggregation and formation of subvisible particles in some of the formulations. This study shows that the effect of commonly used additives on the long-term antibody physical stability can be predicted using orthogonal biophysical measurements.
000429592 536__ $$0G:(DE-HGF)POF3-6G3$$a6G3 - PETRA III (POF3-622)$$cPOF3-622$$fPOF III$$x0
000429592 588__ $$aDataset connected to CrossRef
000429592 693__ $$0EXP:(DE-H253)P-P12-20150101$$1EXP:(DE-H253)PETRAIII-20150101$$6EXP:(DE-H253)P-P12-20150101$$aPETRA III$$fPETRA Beamline P12$$x0
000429592 7001_ $$aKulakova, Alina$$b1
000429592 7001_ $$aZalar, Matja$$b2
000429592 7001_ $$aGolovanov, Alexander P.$$b3
000429592 7001_ $$0P:(DE-H253)PIP1080794$$aHarris, Pernille$$b4
000429592 7001_ $$aWinter, Gerhard$$b5
000429592 8564_ $$uhttps://epub.ub.uni-muenchen.de/69721/
000429592 8564_ $$uhttps://bib-pubdb1.desy.de/record/429592/files/Orthogonal_Winter.pdf$$yPublished on 2019-11-02. Available in OpenAccess from 2020-11-02.$$zStatID:(DE-HGF)0510
000429592 8564_ $$uhttps://bib-pubdb1.desy.de/record/429592/files/PIIS0022354919307373.pdf$$yRestricted$$zStatID:(DE-HGF)0599
000429592 8564_ $$uhttps://bib-pubdb1.desy.de/record/429592/files/Orthogonal_Winter.gif?subformat=icon$$xicon$$yPublished on 2019-11-02. Available in OpenAccess from 2020-11-02.$$zStatID:(DE-HGF)0510
000429592 8564_ $$uhttps://bib-pubdb1.desy.de/record/429592/files/Orthogonal_Winter.jpg?subformat=icon-1440$$xicon-1440$$yPublished on 2019-11-02. Available in OpenAccess from 2020-11-02.$$zStatID:(DE-HGF)0510
000429592 8564_ $$uhttps://bib-pubdb1.desy.de/record/429592/files/Orthogonal_Winter.jpg?subformat=icon-180$$xicon-180$$yPublished on 2019-11-02. Available in OpenAccess from 2020-11-02.$$zStatID:(DE-HGF)0510
000429592 8564_ $$uhttps://bib-pubdb1.desy.de/record/429592/files/Orthogonal_Winter.jpg?subformat=icon-640$$xicon-640$$yPublished on 2019-11-02. Available in OpenAccess from 2020-11-02.$$zStatID:(DE-HGF)0510
000429592 8564_ $$uhttps://bib-pubdb1.desy.de/record/429592/files/Orthogonal_Winter.pdf?subformat=pdfa$$xpdfa$$yPublished on 2019-11-02. Available in OpenAccess from 2020-11-02.$$zStatID:(DE-HGF)0510
000429592 8564_ $$uhttps://bib-pubdb1.desy.de/record/429592/files/PIIS0022354919307373.gif?subformat=icon$$xicon$$yRestricted$$zStatID:(DE-HGF)0599
000429592 8564_ $$uhttps://bib-pubdb1.desy.de/record/429592/files/PIIS0022354919307373.jpg?subformat=icon-1440$$xicon-1440$$yRestricted$$zStatID:(DE-HGF)0599
000429592 8564_ $$uhttps://bib-pubdb1.desy.de/record/429592/files/PIIS0022354919307373.jpg?subformat=icon-180$$xicon-180$$yRestricted$$zStatID:(DE-HGF)0599
000429592 8564_ $$uhttps://bib-pubdb1.desy.de/record/429592/files/PIIS0022354919307373.jpg?subformat=icon-640$$xicon-640$$yRestricted$$zStatID:(DE-HGF)0599
000429592 8564_ $$uhttps://bib-pubdb1.desy.de/record/429592/files/PIIS0022354919307373.pdf?subformat=pdfa$$xpdfa$$yRestricted$$zStatID:(DE-HGF)0599
000429592 909CO $$ooai:bib-pubdb1.desy.de:429592$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000429592 915__ $$0StatID:(DE-HGF)0530$$2StatID$$aEmbargoed OpenAccess
000429592 915__ $$0StatID:(DE-HGF)0550$$2StatID$$aNo Authors Fulltext
000429592 915__ $$0StatID:(DE-HGF)0580$$2StatID$$aPublished
000429592 9141_ $$y2019
000429592 9101_ $$0I:(DE-588b)235011-7$$6P:(DE-H253)PIP1080794$$aEuropean Molecular Biology Laboratory$$b4$$kEMBL
000429592 9101_ $$0I:(DE-HGF)0$$6P:(DE-H253)PIP1080794$$aExternal Institute$$b4$$kExtern
000429592 9131_ $$0G:(DE-HGF)POF3-622$$1G:(DE-HGF)POF3-620$$2G:(DE-HGF)POF3-600$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF3-6G3$$aDE-HGF$$bForschungsbereich Materie$$lVon Materie zu Materialien und Leben$$vFacility topic: Research on Matter with Brilliant Light Sources$$x0
000429592 9201_ $$0I:(DE-H253)EMBL-User-20120814$$kEMBL-User$$lEMBL-User$$x0
000429592 980__ $$apreprint
000429592 980__ $$aVDB
000429592 980__ $$aUNRESTRICTED
000429592 980__ $$aI:(DE-H253)EMBL-User-20120814
000429592 9801_ $$aFullTexts