Case Studies Involving Protein Aggregation

Aggregation of Therapeutic Proteins

Volumn , Issue , 2010, Pages 367-401

  Rajan, Rahul S ^a   Li, Tiansheng ^b   Arakawa, Tsutomu ^c  

^a AMGEN INC   (United States)

^b HTL Biosolutions Inc   (United States)

^c ALLIANCE PROTEIN LABORATORIES   (United States)

Author keywords

Aggregation in frozen state role of excipient crystallization; Protein aggregation, complex degradation pathway universal phenomenon in vivo and in vitro; Protein therapeutics, lyophilized for acceptable shelf life

Indexed keywords

EID: 80052973341     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470769829.ch9     Document Type: Chapter

References (73)

1. Dobson CM. 2004. Principles of protein folding, misfolding and aggregation. Semin Cell Dev Biol 15: 3-16.
2. Wang W, Singh S, Zeng DL, King K, Nema S. 2007. Antibody structure, instability and formulation. J Pharm Sci 96: 1-26.
3. Rathore N, Rajan RS. 2008. Current perspectives on stability of protein drug products during formulation, fill and finish operations. Biotechnol Prog 24: 504-514.
4. Dobson CM. 2006. Protein aggregation and its consequences for human disease. Protein Pept Lett 13: 219-227.
5. Chen S, Ferrone FA, Wetzel R. 2002. Huntington ' s disease age-of-onset linked to polyglutamine aggregation nucleation. Proc Natl Acad Sci U S A 99: 11884-11889.
6. Illing ME, Rajan RS, Bence NF, Kopito RR. 2002. A rhodopsin mutant linked to autosomal dominant retinitis pigmentosa is prone to aggregate and interacts with the ubiquitin proteasome system. J Biol Chem 277: 34150-34160.
7. Rosenberg AS. 2006. Effects of protein aggregates: An immunologic perspective. AAPS J 8: E501-E507.
8. Janeway CA, Travers PA, Walport M, Shlomchik MJ. 2001. Immunobiology. New York: Garland Publishing.
9. Lumry R, Eyring HJ. 1954. Conformational changes of proteins. J Phys Chem 58: 110-120.
10. Arakawa T, Kita Y, Carpenter JF. 1991. Protein-solvent interactions in pharmaceutical formulations. Pharm Res 8 (3): 285-291.
11. Gekko K, Timasheff SN. 1981. Mechanism of protein stabilization by glycerol: Preferential hydration in glycerol-water mixtures. Biochemistry 20 (16): 4667-4676.
12. Lee JC, Timasheff SN. 1981. The stabilization of proteins by sucrose. J Biol Chem. 256(14): 7193-7201.
13. Yancey PH, Clark ME, Hand SC, Bowlus RD, Somero GN. 1982. Living with water stress: Evolution of osmolyte systems. Science 217 (4566): 1214-1222.
14. Milner JL, McClellan DJ, Wood JM. 1987. Factors reducing and promoting the effectiveness of proline as an osmoprotectant in Escherichia coli K12. J Gen Microbiol 133 (7): 1851-1860.
15. Soler PM, Wright TE, Smith PD, Maggi SP, Hill DP, Ko F, Jimenez PA, Robson MC. 1999. In vivo characterization of keratinocyte growth factor-2 as a potential wound healing agent. Wound Repair Regen 7 (3): 172-178.
16. Gomperts BN, Belperio JA, Fishbein MC, Keane MP, Burdick MD, Strieter RM. Keratinocyte growth factor improves repair in the injured tracheal epithelium. Am J Respir Cell Mol Biol 37 (1): 48-56.
17. Osslund TD, Syed R, Singer E, Hsu EW, Nybo R, Chen BL, Harvey T, Arakawa T, Narhi LO, Chirino A, Morris CF. 1998. Correlation between the 1.6 A crystal structure and mutational analysis of keratinocyte growth factor. Protein Sci. 7(8): 1681-1690.
18. Chen BL, Arakawa T, Hsu E, Narhi LO, Tressel TJ, Chien SL. 1994. Strategies to suppress aggregation of recombinant keratinocyte growth factor during liquid formulation development. J Pharm Sci 83 (12): 1657-1661.
19. Chen BL, Arakawa T. 1996. Stabilization of recombinant human keratinocyte growth factor by osmolytes and salts. J Pharm Sci. 85 (4): 419-426.
20. Back JF, Oakenfull D, Smith MB. 1979. Increased thermal stability of proteins in the presence of sugars and polyols. Biochemistry 18 (23): 5191-5196.
21. Arakawa T, Timasheff SN. 1985. The stabilization of protein by osmolytes. Biophys J 47: 411-414.
22. Kendrick BS, Carpenter JF, Cleland JL, Randolph TW. 1998. A transient expansion of the native state precedes aggregation of recombinant human interferon -gamma. Proc Natl Acad Sci U S A 95 (24): 14142-14146.
23. Tiwari A, Bhat R. 2006. Stabilization of yeast hexokinase A by polyol osmolytes: Correlation with the physicochemical properties of aqueous solutions. Biophys Chem 124 (2): 90-99.
24. Krishnan S, Chi EY, Webb JN, Chang BS, Shan D, Goldenberg M, Manning MC, Randolph TW, Carpenter JF. 2002. Aggregation of granulocyte colony stimulating factor under physiological conditions: Characterization and thermodynamic inhibition. Biochemistry 41 (20): 6422-6431.
25. Timasheff SN. 1998. Control of protein stability and reactions by weakly interacting cosolvents: The simplicity of the complicated. Adv Protein Chem 51: 355-432.
26. Timasheff SN. 2002. Protein-solvent preferential interactions, protein hydration, and the modulation of biochemical reactions by solvent components. Proc Natl Acad Sci U S A 99 (15): 9721-9726.
27. Timasheff SN. 2002. Thermodynamic binding and site occupancy in the light of the Schellman exchange concept. Biophys Chem 101-102: 99-111.
28. Timasheff SN. 2002. Protein hydration, thermodynamic binding, and preferential hydration. Biochemistry 41 (46): 13473-13482.
29. Arakawa T, Tsumoto K, Kita Y, Chang B, Ejima D. 2007. Biotechnology applications of amino acids in protein purification and formulations. Amino Acids. 33(4): 587-605.
30. Arakawa T, Timasheff SN. 1983. Preferential interactions of proteins with solvent components in aqueous amino acid solutions. Arch Biochem Biophys 224 (1): 169-177.
31. Arakawa T, Kita Y, Timasheff SN. 2007. Protein precipitation and denaturation by dimethyl sulfoxide. Biophys Chem 131: 62-70.
32. Fujita Y, Noda Y. 1983. The effect of organic solvents on the thermal denaturation of lysozyme as measured by differential scanning calorimetry. Bull Chem Soc Jpn. 56 (1): 233-237.
33. Carpenter JF, Arakawa T, Crowe JH. 1992. Interactions of stabilizing additives with proteins during freeze-thawing and freeze-drying. Dev Biol Stand 74: 225-238.
34. Klibanov AM. 2001. Improving enzymes by using them in organic solvents. Nature 409 (6817): 241-246.
35. Perico N, Purtell J, Dillon TM, Ricci MS. 2008. Conformational implications of an inversed pH-dependent antibody aggregation. J Pharm Sci. September 19. Epub ahead of print.
36. Chang BS, Hershenson S. 2002. Practical approaches to protein formulation development. Pharm Biotechnol 13: 1-25.
37. Geigel MA. 2003. The stability testing program. In Medina C, ed., Compliance Handbook for Pharmaceuticals, Medical Devices and Biologics, Part of Drug and Pharmaceutical Sciences, Vol. 136. New York: Informa Healthcare.
38. Philo JS. 2006. Is any measurement method optimal for all aggregate sizes and types? AAPS J 8: E564-E571.
39. Alexander AJ, Hughes DE. 1995. Monitoring of IgG antibody thermal stability by micellar electrokinetic capillary chromatography and matrix-assisted laser desorption/ ionization mass spectrometry. Anal Chem 67: 3626-3632.
40. Wypych J, Li M, Guo A, Zhang Z, Martinez T, Allen MJ, Fodor S, Kelner DN, Flynn GC, Liu YD, Bondarenko PV, Ricci MS, Dillon TM, Balland A. 2008. Human IgG2 antibodies display disulfide mediated structural isoforms. J Biol Chem 283: 16194-16205.
41. Dillon TM, Ricci MS, Vezina C, Flynn GC, Liu YD, Rehder DS, Plant M, Henkle B, Li Y, Deechongkit S, Varnum B, Wypych J, Balland A, Bondarenko PV. 2008. Structural and functional characterization of disulfide isoforms of the human IgG2 subclass. J Biol Chem 283: 16206-16215.
42. Piedmonte DM, Summers C, McAuley A, Karamujic L, Ratnaswamy G. 2007. Sorbitol crystallization can lead to protein aggregation in frozen protein formulations. Pharm Res 24: 136-146.
43. Yancey PH. 2005. Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses. J Exp Biol 208: 2819-2830.
44. Arakawa T, Timasheff SN. 1982. Stabilization of protein by sugars. Biochemistry 21: 6536-6544.
45. Carpenter JF, Crowe JH. 1988. The mechanism of cryoprotection of proteins by solutes. Cryobiology 25 (3): 244-255.
46. Bhatnagar BS, Pikal MJ, Bogner RH. 2008. Study of the individual contributions of ice formation and freeze-concentration on isothermal stability of lactate dehydrogenase during freezing. J Pharm Sci 97 (2): 798-814.
47. Breen ED, Curley JG, Overcashier DE, Hsu CC, Shire SJ. 2001. Effect of moisture on the stability of a lyophilized humanized monoclonal antibody formulation. Pharm Res 18: 1345-1353.
48. Andya JD, Hsu CC, Shire SJ. 2003. Mechanisms of aggregate formation and carbohydrate excipient stabilization of lyophilized humanized monoclonal antibody formulations. AAPS PharmSci 5: E10.
49. Careri G, Gratton E, Yang PH, Rupley JA. 1980. Correlation of IR spectroscopic, heat capacity, diamagnetic susceptibility and enzymatic measurements on lysozyme powder. Nature 284: 572-573.
50. Wang W. 1999. Instability, stabilization and formulation of liquid protein pharmaceuticals. Int J Pharm 185: 125-188.
51. Carpenter JF, Chang BS, Garzon-Rodriguez W, Randolph TW. 2002. Rational design of stable lyophilized protein formulations: Theory and practice. Pharm Biotechnol 13: 109-133.
52. Lu X, Pikal MJ. 2004. Freeze-drying of mannitol-trehalose-sodium chloride-based formulations: The impact of annealing on dry layer resistance to mass transfer and cake structure. Pharm Dev Technol 9: 85-95.
53. Carpenter JF, Pikal MJ, Chang BS, Randolph TW. 1997. Rational design of stable lyophilized protein formulations: some practical advice. Pharm Res 14: 969-975.
54. Arakawa T, Prestrelski SJ, Kenney WC, Carpenter JF. 2001. Factors affecting short-term and long-term stabilities of proteins. Adv Drug Deliv Rev 46: 307-326.
55. Carpenter JF, Izutsu K-I, Randolph TW. 2004. Freezing-and drying-induced perturbations of protein structure and mechanisms of protein protection by stabilizing additives. (Freeze-Drying/Lyophilization of Pharmaceutical and Biological Products). Drugs Pharm Sci 137: 147-186.
56. Pikal MJ. 1994. Freeze-drying of proteins: Process, formulation, and stability. ACS Symp Ser (Formulation and Delivery of Proteins and Peptides) 567: 20-133.
57. Andya JD, Maa YF, Costantino HR, Nguyen PA, Dasovich N, Sweeney TD, Hsu CC, Shire SJ. 1999. The effect of formulation excipients on protein stability and aerosol performance of spray-dried powders of a recombinant humanized anti-IgE monoclonal antibody. Pharm Res 16: 350-358.
58. Cleland JL, Lam X, Kendrick B, Yang J, Yang TH, Overcashier D, Brooks D, Hsu C, Carpenter JF. 2001. A specific molar ratio of stabilizer to protein is required for storage stability of a lyophilized monoclonal antibody. J Pharm Sci 90: 310-321.
59. Pikal MJ, Dellerman K, Roy ML. 1992. Formulation and stability of freeze-dried proteins: Effects of moisture and oxygen on the stability of freeze-dried formulations of human growth hormone. Dev Biol Stand 74: 21-37.
60. Huang K, Dong J, Phillips NB, Carey PR, Weiss MA. 2003 Pro-insulin is refractory to protein fibrillation. J Biol Chem 280: 42345-42355.
61. Hua QX, Weiss MA. 2004. Mechanism of insulin fibrillation: The structure of insulin under amyloidogenic conditions resembles a protein-folding. J Biol Chem 279: 21449-21460.
62. Przybycien TM, Dunn JP, Valax P, Georgiou G. 1994. Secondary structure characterization of ß-lactamase inclusion bodies. Protein Eng 7: 131-136.
63. Li T, Talvenheimo L, Zeni L, Rosenfeld R, Stearns G, Arakawa T. 2002. Changes in protein conformation and dynamics upon formation of brain-derived neurotrophic factor and its receptor. Biopolymers 67: 10-19.
64. Ejima D, Tsumoto K, Fukada H, Yumioka R, Nagase K, Arakawa T, Philo J. 2007. Effects of acid exposure on the conformation, stability, and aggregation of monoclonal antibodies. Proteins 66: 954-962.
65. Kim Y, Rose CA, Liu Y, Ozaki, Y, Datta G, Tu AT. 1994. FT-IR and near-infared FT-Raman studies of the secondary structure of insulinotropin in the solid state: a-Helix to ß-sheet conversion induced by phenol and/or by high shear force. J Pharm Sci 83: 1175-1180.
66. Ramachander R, Jiang Y, Li C, Eris T, Young M, Dimitrova M, Narhi L. 2008. Solid state fluorescence of lyophilized proteins. Anal Biochem 376: 173-182.
67. Chang BS, Beauvais RM, Dong AC, Carpenter JF. 1996. Physical factors affecting the storage stability of freeze-dried interleukin-1 receptor antagonist - Glass transition and protein conformation. Arch Biochem Biophys 331: 249-258.
68. Strickley G, Anderson BD. 1997. Solid-state stability of human insulin. 2. Effect of water on reactive intermediate partitioning in lyophiles from pH 2-5 solutions - Stabilization against covalent dimer formation. J Pharm Sci 86: 645-653.
69. Mazzobre MF, Buera MD, Chirife J. 1997. Glass transition and thermal stability of lactase in low-moisture amorphous polymeric matrices. Biotechnol Prog 13: 195-199.
70. Tang X, Pikal MJ. 2004. Design of freeze-drying processes for pharmaceuticals: Practical advice. Pharm Res 21: 191-200.
71. Tyagi AK, Randolph TW, Dong A, Maloney KM, Hitscherich C Jr., Carpenter JF. IgG particle formation during filling pump operation: A case study of heterogeneous nucleation on stainless steel nanoparticles. J Pharm Sci 98: 94-104.
72. Carpenter JF, Randolph TW, Jiskoot W, Crommelin DJ, Middaugh CR, Winter G, Fan YX, Kirshner S, Verthelyi D, Kozlowski S, Clouse KA, Swann PG, Rosenberg A, Cherney B. 2008. Overlooking subvisible particles in therapeutic protein products: Gaps that may compromise product quality. J Pharm Sci. August Epub ahead of print.
73. Kiese S, Papppenberger A, Friess W, Mahler HC. 2008. Shaken, not stirred: Mechanical stress testing of an IgG1 antibody. J Pharm Sci 97: 4347-4366.