Application of a high-throughput relative chemical stability assay to screen therapeutic protein formulations by assessment of conformational stability and correlation to aggregation propensity

Journal of Pharmaceutical Sciences

Volumn 104, Issue 5, 2015, Pages 1632-1640

  Rizzo, Joseph M ^a   Shi, Shuai ^a   Li, Yunsong ^a   Semple, Andrew ^a   Esposito, Jessica J ^a   Yu, Shenjiang ^a   Richardson, Daisy ^a   Antochshuk, Valentyn ^a   Shameem, Mohammed ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Calorimetry (DSC); Chemical denaturation; Circular dichroism; Formulation; Guanidine HCl; Intrinsic fluorescence; Protein aggregation; Protein folding refolding; Robotic automation; Urea

Indexed keywords

AROMATIC AMINO ACID; MONOCLONAL ANTIBODY; PROTEIN; TRYPTOPHAN; PROTEIN AGGREGATE; RECOMBINANT PROTEIN;

ANIMAL CELL; ARTICLE; CIRCULAR DICHROISM; CONTROLLED STUDY; DIFFERENTIAL SCANNING CALORIMETRY; DISULFIDE BOND; FLUORESCENCE; FLUOROMETRY; HIGH THROUGHPUT SCREENING; IONIC STRENGTH; NONHUMAN; PH; PROTEIN AGGREGATION; PROTEIN CONFORMATION; PROTEIN DENATURATION; PROTEIN DEPLETION; PROTEIN STABILITY; PROTEIN STRUCTURE; PROTEIN TERTIARY STRUCTURE; PROTEIN UNFOLDING; THERMODYNAMICS; TITRIMETRY; CHEMISTRY; DRUG SCREENING; MEDICINAL CHEMISTRY; PROCEDURES; SPECTROFLUOROMETRY;

ANTIBODIES, MONOCLONAL; CHEMISTRY, PHARMACEUTICAL; CIRCULAR DICHROISM; DRUG EVALUATION, PRECLINICAL; HIGH-THROUGHPUT SCREENING ASSAYS; PROTEIN AGGREGATES; PROTEIN CONFORMATION; RECOMBINANT PROTEINS; SPECTROMETRY, FLUORESCENCE;

EID: 84926387945     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.24408     Document Type: Article

References (28)

1. Editorial Staff. 2006. Nature Reviews Immunology 6(10):S4. doi:10.1038/nri1946
2. Shire SJ, Shahrokh Z, Liu J. 2004. Challenges in the development of high protein concentration formulations. J Pharm Sci 93:1390-1402.
3. Yeh AP, McMillan A, Stowell MHB. 2006. Rapid and simple proteinstability screens: Application to membrane proteins. Acta Crystallogr D Biol Crystallogr 62:451-457.
4. Matulis D, Kranz JK, Salemme FR, Todd MJ. 2005. Thermodynamic stability of carbonic anhydrase: Measurements of binding affinity and stoichiometry using ThermoFluor. Biochemistry 44(13):5258-5266.
5. Crowther GJ, Napuli AJ, Thomas AP, Chung DJ, Kovzun KV, Leibly DJ, Castaneda LJ, Bhandari J, Damman CJ, Hui R, Hol WGJ, Buckner FS, Verlinde CLMJ, Zhang ZS, Fan EK, Van Voorhis WC. 2009. Buffer optimization of thermal melt assays of plasmodium proteins for detection of small-molecule ligands. J Biomol Screen 14(6):700-707.
6. Ericsson UB, Hallberg BM, DeTitta GT, Dekker N, Nordlund P. 2006. Thermofluor-based high-throughput stability optimization of proteins for structural studies. Anal Biochem 357(2):289-298.
7. Vedadi M, Niesen FH, Allali-Hassani A, Fedorov OY, Finerty PJ, Wasney GA, Yeung R, Arrowsmith C, Ball LJ, Berglund H, Hui R, Marsden BD, Nordlund P, Sundstrom M, Weigelt J, Edwards AM. 2006. Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination. Proc Natl Acad Sci USA 103(43):15835-15840.
8. Yamniuk A, Ditto N, Patel M, Dai J, Sejwal P, Stetsko P, Doyle M. 2013. Application of a kosmotrope-based solubility assay to multiple protein therapeutic classes indicates broad use as a high-throughput screen for protein therapeutic aggregation propensity. J Pharm Sci 102(8):2424-2439.
9. Santoro MM, Bolen DW. 1988. Unfolding free energy changes determined by the linear extrapolation method. 1. Unfolding of phenylmethanesulfonyl alpha-chymotrypsin using different denaturants. Biochemistry 27:8063-8068.
10. Greene RF Jr, Pace CN. 1974. Urea and guanidine hydrochloride denaturation of ribonuclease, lysozyme, alpha-chymotrypsin, and beta-lactoglobulin. J Biol Chem 249:5388-5393.
11. Pace CN, Laurents DV, Erickson RE. 1992. Urea denaturation of barnase: pH dependence and characterization of the unfolded state. Biochemistry 31:2728-2734.
12. Bolen DW, Santoro MM. 1988. Unfolding free energy changes determined by the linear extrapolation method. 2. Incorporation of dGn-u values in a thermodynamic cycle. Biochemistry 27:8069-8074.
13. Myers JK, Pace CN, Scholtz JM. 1995. Denaturant m values and heat capacity changes: Relation to changes in accessible surface area of protein unfolding. Prot Sci 4:2138-2148.
14. Robertson A, Murphy K. 1997. Protein structure and the energetics of protein stability. Chem Rev 97:1251-1267.
15. Alder AJ, Greenfield NJ, Fasman GD. 1973. Circular dichroism and optical rotatory dispersion of proteins and polypeptides. Methods Enzymol 27:675.
16. Pace C. 1986. Determination and analysis of urea and guanidine hydrochloride denaturation curves. Methods Enzymol 131:266-280.
17. DeKoster GT, Robertson AD, Stock AM, Stock JB. 1993. Urea and guanidine-HCl yield different unfolding free energies for CheY: Which denaturant provides the most reliable free energy values? Tech Protein Chem IV:533-540.
18. Buckley D, Whitney P, Tanford C. 1963. The unfolding and renaturation of a specific univalent antibody fragment. Biochemistry 50:827-834.
19. Greenstein J. 1939. Sulfhydryl groups in proteins: II. Edestin, Excelsin, and Globin in solutions of guanidine hydrochloride, urea, and their derivatives. J Biol Chem 128:233-240.
20. Menzen T, Friess W. 2012. High-throughput melting-temperature analysis of a monoclonal antibody by differential scanning fluorimetry in the presence of surfactants. J Pharm Sci 102:415-428.
21. He F, Hogan S, Latypov RF, Narhi LO, Razinkov VI. 2010. High throughput thermostability screening of monoclonal antibody formulations. J Pharm Sci 99(4):1707-1720.
22. Harn N, Allan C, Oliver C, Middaugh CR. 2007. Highly concentrated monoclonal antibody solutions: Direct analysis of physical structure and thermal stability. J Pharm Sci 96(3):532-546.
23. Freire E, Arne S, Hutchins B, Brown R. 2013. Chemical denaturation as a tool in the formulation optimization of biologics. Drug Discov Today 18(19-20):107-113.
24. Shi S, Semple A, Cheung J, Shameem M. 2013. DSF method optimization and its application in predicting protein thermal aggregation kinetics. J Pharm Sci 102:2471-2483.
25. Monera OD, Kay CM, Hodges RS. 1994. Protein denaturation with guanidine hydrochloride or urea provides a different estimate of stability depending on the contribution of electrostatic interactions. Protein Sci 3:1984-1991.
26. Wu JW, Wang ZX. 1999. New evidence for the denaturant binding model. Protein Sci 10:2090-2097.
27. Roberts C, Das T, Sahin E. 2011. Predicting solution aggregation rates for therapeutic proteins: Approaches and challenges. Int J Pharm 418:318-333.
28. th ed. United Kingdom University of Southampton, Copyright BMJ Publishing Group.