Aggregation, stability, and formulation of human antibody therapeutics

Advances in Protein Chemistry and Structural Biology

Volumn 84, Issue , 2011, Pages 41-61

  Lowe, D ^a   Dudgeon, K ^b   Rouet, R ^b   Schofield, P ^b   Jermutus, L ^a   Christ, D ^b,c  

^a MEDIMMUNE   (United States)

^b GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

^c UNIVERSITY OF NEW SOUTH WALES   (Australia)

Author keywords

Antibody engineering; Antibody fragments; Formulation; Protein aggregation; Protein stability; Variable domains

Indexed keywords

EID: 80051910636     PISSN: 18761623     EISSN: None     Source Type: Book Series    
DOI: 10.1016/B978-0-12-386483-3.00004-5     Document Type: Chapter

References (73)

1. J.D. Andya, C.C. Hsu, and S.J. Shire Mechanisms of aggregate formation and carbohydrate excipient stabilization of lyophilized humanized monoclonal antibody formulations AAPS Pharm. Sci. 5 2003 1 11
2. T. Arakawa, D. Ejima, T. Li, and J.S. Philo The critical role in mobile phase composition in size exclusion chromatography of protein pharmaceuticals J. Pharm. Sci. 99 2010 1674 1692
3. P.A. Barthelemy, H. Raab, B.A. Appleton, C.J. Bond, P. Wu, and C. Wiesmann Comprehensive analysis of the factors contributing to the stability and solubility of autonomous human VH domains J. Biol. Chem. 283 2008 3639 3654
4. S.A. Berkowitz Role of analytical ultracentrifugation in assessing the aggregation of protein biopharmaceuticals AAPS J. 8 2006 590 605
5. J. Birch, and A. Racher Antibody production Adv. Drug Deliv. Rev. 58 2006 671 685 (Pubitemid 44247226)
6. J. Buchner, U. Brinkmann, and I. Pastan Renaturation of a single-chain immunotoxin facilitated by chaperones and protein disulfide isomerase Biotechnology (NY) 10 1992 682 685
7. J. Buchner, I. Pastan, and U. Brinkmann A method for increasing the yield of properly folded recombinant fusion proteins: single-chain immunotoxins from renaturation of bacterial inclusion bodies Anal. Biochem. 205 1992 263 270
8. S. Cabilly, A.D. Riggs, H. Pande, J.E. Shively, W.E. Holmes, and M. Rey Generation of antibody activity from immunoglobulin polypeptide chains produced in Escherichia coli Proc. Natl. Acad. Sci. USA 81 1984 3273 3277 (Pubitemid 14123420)
9. M.A.H. Capelle, R. Gurny, and T. Arvinte High throughput screening of protein formulation stability: practical considerations Eur. J. Pharm. Biopharm. 65 2007 131 148 (Pubitemid 46038086)
10. N. Chennamsetty, V. Voynov, V. Kayser, B. Helk, and B.L. Trout Design of therapeutic proteins with enhanced stability Proc. Natl. Acad. Sci. USA 106 2009 11937 11942
11. F. Chiti, M. Stefani, N. Taddei, G. Ramponi, and C.M. Dobson Rationalization of the effects of mutations on peptide and protein aggregation rates Nature 424 2003 805 808 (Pubitemid 37021713)
12. D. Christ, K. Famm, and G. Winter Tapping diversity lost in transformations - in vitro amplification of ligation reactions Nucleic Acids Res. 34 2006 el08
13. D. Christ, K. Famm, and G. Winter Repertoires of aggregation-resistant human antibody domains Protein Eng. Des. Sel. 20 2007 413 416 (Pubitemid 47428968)
14. R.V. Cordoba-Rodriguez Aggregates in mAbs and recombinant therapeutic proteins: a regulatory perspective BioPharm. Int. 21 2008 44 53
15. J. Davies, and L. Riechmann 'Camelising' human antibody fragments: NMR studies on VH domains FEBS Lett. 339 1994 285 290 (Pubitemid 24063464)
16. S.J. Demarest, and S.M. Glaser Antibody therapeutics, antibody engineering, and the merits of protein stability Curr. Opin. Drug Discov. Devel. 11 5 2008 675 687
17. N. Dimasi, C. Gao, R. Fleming, R.M. Woods, X.T. Yao, and L. Shirinian The design and characterization of oligospecific antibodies for simultaneous targeting of multiple disease mediators J. Mol. Biol. 393 2009 672 692
18. K. Dudgeon, K. Famm, and D. Christ Sequence determinants of protein aggregation in human VH domains Protein Eng. Des. Sel. 22 2009 217 220
19. S. Ewert, C. Cambillau, K. Conrath, and A. Pluckthun Biophysical properties of camelid V(HH) domains compared to those of human V(H)3 domains Biochemistry 41 2002 3628 3636 (Pubitemid 34224675)
20. S. Ewert, A. Honegger, and A. Pluckthun Structure-based improvement of the biophysical properties of immunoglobulin VH domains with a generalizable approach Biochemistry 42 2003 1517 1528 (Pubitemid 36205958)
21. S. Ewert, T. Huber, A. Honegger, and A. Pluckthun Biophysical properties of human antibody variable domains J. Mol. Biol. 325 2003 531 553 (Pubitemid 36062681)
22. K. Famm, L. Hansen, D. Christ, and G. Winter Thermodynamically stable aggregation-resistant antibody domains through directed evolution J. Mol. Biol. 376 2008 926 931
23. A.M. Fernandez-Escamilla, F. Rousseau, J. Schymkowitz, and L. Serrano Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins Nat. Biotechnol. 22 2004 1302 1306 (Pubitemid 39336784)
24. H. Franey, S.R. Brych, C.G. Kolvenbach, and R.S. Rajan Increased aggregation propensity of IgG2 subclass over IgG1: role of conformational changes and covalent character in isolated aggregates Protein Sci. 19 2010 1601 1615
25. J.P. Gabrielson, K.K. Arthur, M.R. Stoner, B.C. Winn, B.S. Kendrick, and V. Razinkov Precision of protein aggregation measurements by sedimentation velocity analytical ultracentrifugation in biopharmaceutical applications Anal. Biochem. 396 2010 231 241
26. D.S. Goldberg, S.M. Bishop, A.U. Shah, and H.A. Sathish Formulation development of therapeutic monoclonal antibodies using high-throughput fluorescence and static light scattering techniques: Role of conformational and colloidal stability J. Pharm. Sci. 2010
27. C. Hamers-Casterman, T. Atarhouch, S. Muyldermans, G. Robinson, C. Hamers, and E.B. Songa Naturally occurring antibodies devoid of light chains Nature 363 1993 446 448 (Pubitemid 23179389)
28. N. Harn, C. Allan, C. Oliver, and C.R. Middaugh Highly concentrated monoclonal antibody solutions: direct analysis of physical structure and thermal stability J. Pharm. Sci. 96 2007 532 546 (Pubitemid 46466076)
29. F. He, S. Hogan, R.F. Latypov, L.O. Narhi, and V.I. Razinkov High throughput thermostability screening of monoclonal antibody formulations J. Pharm. Sci. 99 2009 1707 1720
30. R.M. Ionescu, J. Vlasak, C. Price, and M. Kirchmeier Contribution of variable domains to the stability of humanized IgG1 monoclonal antibodies J. Pharm. Sci. 97 2008 114 1426
31. I. Jelesarov, and H.R. Bosshard Isothermal titration calorimetry and differential scanning calorimetry as complementary tools to investigate the energetics of biomolecular recognition J. Mol. Recognit. 12 1999 3 18 (Pubitemid 29160432)
32. N. Jenkins, L. Murphy, and R. Tyther Post-translational modifications of recombinant proteins: significance for biopharmaceuticals Mol. Biotechnol. 38 2008 113 118
33. L. Jespers, O. Schon, K. Famm, and G. Winter Aggregation-resistant domain antibodies selected on phage by heat denaturation Nat. Biotechnol. 22 2004 1161 1165 (Pubitemid 39166856)
34. L. Jespers, O. Schon, L.C. James, D. Veprintsev, and G. Winter Crystal structure of HEL4, a soluble, refoldable human V(H) single domain with a germ-line scaffold J. Mol. Biol. 337 2004 893 903 (Pubitemid 38368933)
35. B. Kelley Industrialization of mAb production technology - the bioprocessing industry at a crossroads MAbs 1 2009 1 10
36. A.F. Labrijn, A.O. Buijsse, E.T. van den Bremer, A.Y. Verwilligen, W.K. Bleeker, and S.J. Thorpe Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo Nat. Biotechnol. 27 2009 767 771
37. A. Lahlou, B. Blanchet, M. Carvalho, M. Paul, and A. Astier Mechanically-induced aggregation of the monoclonal antibody cetuximab Ann. Pharm. Fr. 67 2009 340 352
38. C.M. Lee, N. Iorno, F. Sierro, and D. Christ Selection of human antibody fragments by phage display Nat. Protoc. 2 2007 3001 3008
39. C.M. Lee, H. McGuire, A. Basten, C. King, and D. Christ Expression, purification and characterization of recombinant interleukin-21 J. Immunol. Methods 362 2010 185 189
40. H. Lilie, K. Lang, R. Rudolph, and J. Buchner Prolyl isomerases catalyze antibody folding in vitro Protein Sci. 2 1993 1490 1496 (Pubitemid 23262841)
41. M.C. Manning, J.E. Matsuura, B.S. Kendrick, J.D. Meyer, J.J. Dormish, and M. Vrkljan Approaches for increasing the solution stability of proteins Biotechnol. Bioeng. 48 1995 506 512
42. C.D. Martin, G. Rojas, J.N. Mitchell, K.J. Vincent, J. Wu, and J. McCafferty A simple vector system to improve performance and utilisation of recombinant antibodies BMC Biotechnol. 6 2006 46
43. K.D. Miller, J. Weaver-Feldhaus, S.A. Gray, R.W. Siegel, and M.J. Feldhaus Production, purification, and characterization of human scFv antibodies expressed in Saccharomyces cerevisiae, Pichia pastoris, and Escherichia coli Protein Expr. Purif. 42 2005 255 267 (Pubitemid 40985019)
44. M. Molinari, and A. Helenius Chaperone selection during glycoprotein translocation into the endoplasmic reticulum Science 288 2000 331 333 (Pubitemid 30226193)
45. A.L. Nelson, E. Dhimolea, and J.M. Reichert Development trends for human monoclonal antibody therapeutics Nat. Rev. Drug Discov. 9 2010 767 774
46. U. Nobbmann, M. Connah, B. Fish, P. Varley, C. Gee, and S. Mulot Dynamic light scattering as a relative tool for assessing the molecular integrity and stability of monoclonal antibodies Biotechnol. Genet. Eng. Rev. 24 2007 117 128 (Pubitemid 350032945)
47. M. Paborji, N.L. Pochopin, W.P. Coppola, and J.B. Bogardus Chemical and physical stability of chimeric L6, a mouse-human monoclonal antibody Pharm. Res. 11 1994 764 771 (Pubitemid 24171776)
48. E.A. Padlan Anatomy of the antibody molecule Mol. Immunol. 31 1994 169 217 (Pubitemid 24071681)
49. M.W. Pantoliano, E.C. Petrella, J.D. Kwasnoski, V.S. Lobanov, J. Myslik, and E. Graf High-density miniaturized thermal shift assays as a general strategy for drug discovery J. Biomol. Screen. 6 2001 429 440 (Pubitemid 34052847)
50. R.B. Pepinsky, L. Silvian, S.A. Berkowitz, G. Farrington, A. Lugovskoy, and L. Walus Improving the solubility of anti-LINGO-1 monoclonal antibody Li33 by isotype switching and targeted mutagenesis Protein Sci. 19 2010 954 966
51. J.S. Philo Is any measurement optimal for all aggregate sizes and types? AAPS J. 8 2006 564 571 (Pubitemid 44399103)
52. B.E. Power, N. Ivancic, V.R. Harley, R.G. Webster, A.A. Kortt, and R.A. Irving High-level temperature-induced synthesis of an antibody VH-domain in Escherichia coli using the PelB secretion signal Gene 113 1992 95 99
53. L. Riechmann Rearrangement of the former VL interface in the solution structure of a camelised, single antibody VH domain J. Mol. Biol. 259 1996 957 969 (Pubitemid 26229862)
54. D. Rothlisberger, A. Honegger, and A. Pluckthun Domain interactions in the Fab fragment: a comparative evaluation of the single-chain Fv and Fab format engineered with variable domains of different stability J. Mol. Biol. 347 2005 773 789 (Pubitemid 40357919)
55. J.J. Schwegman, J.F. Carpenter, and S.L. Nail Evidence of partial unfolding of proteins at the ice/freeze-concentrate interface by infrared microscopy J. Pharm. Sci. 98 2009 3239 3246
56. G.A. Senisterra, E. Markin, K. Yamazaki, R. Hui, M. Vedadi, and D.E. Awrey Screening for ligands using a generic and high-throughput light-scattering-based assay J. Biomol. Screen. 11 2006 940 948 (Pubitemid 44847148)
57. S.J. Shire, Z. Shahrokh, and J. Liu Challenges in the development of high protein concentration formulations J. Pharm. Sci. 93 2004 1390 1402 (Pubitemid 38725014)
58. A.A. Shukla, and J. Thömmes Recent advances in large-scale production of monoclonal antibodies and related proteins Trends Biotechnol. 28 5 2009 253 261
59. S.K. Singh, N. Rathore, A. McAuley, and A.S. Rathore Best practices for formulation and manufacturing of biotech drug products BioPharm. Int. 22 2009 32 48
60. A. Skerra, and A. Pluckthun Assembly of a functional immunoglobulin Fv fragment in Escherichia coli Science 240 1988 1038 1041
61. D. Steiner, P. Forrer, M.T. Stumpp, and A. Pluckthun Signal sequences directing cotranslational translocation expand the range of proteins amenable to phage display Nat. Biotechnol. 24 2006 823 831 (Pubitemid 44086624)
62. C. Taggart, D. Carvantes-Laurean, G. Kim, N.G. McElvaney, N. Wehr, and J. Moss Oxidation of either methionine 351 or methionine 358 in alpha 1-antitrypsin causes loss of anti-neutrophil elastase activity J. Biol. Chem. 275 2000 27258 27265
63. T. Tanaka, G.T. Chung, A. Forster, M.N. Lobato, and T.H. Rabbitts De novo production of diverse intracellular antibody libraries Nucleic Acids Res. 31 2003 e23
64. G.G. Tartaglia, A. Cavalli, R. Pellarin, and A. Caflisch Prediction of aggregation rate and aggregation-prone segments in polypeptide sequences Protein Sci. 14 2005 2723 2734 (Pubitemid 41395598)
65. T. Teerinen, J. Valjakka, J. Rouvinen, and K. Takkinen Structure-based stability engineering of the mouse IgG1 Fab fragment by modifying constant domains J. Mol. Biol. 361 2006 687 697 (Pubitemid 44177743)
66. K. Tsumoto, D. Ejima, Y. Kita, and T. Arakawa Why is arginine effective in suppressing aggregation? Protein Pept. Lett. 12 2005 613 619 (Pubitemid 41305816)
67. A. Usami, A. Ohtsu, S. Takahama, and T. Fujii The effect of pH, hydrogen peroxide and temperature on stability of human monoclonal antibody J. Pharm. Biomed. Anal. 14 1997 1133 1140
68. M. van der Neut Kolfschoten, J. Schuurman, M. Losen, W.K. Bleeker, P. Martinez-Martinez, and E. Vermeulen Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange Science 317 2007 1554 1557 (Pubitemid 47417435)
69. M. Vedadi, F.H. Niesen, A. Allali-Hassani, O.Y. Fedorov, P.J. Finerty, and G.A. Wasney Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination Proc. Natl. Acad. Sci. USA 103 2006 15835 15840 (Pubitemid 44657553)
70. V. Voynov, N. Chennamsetty, V. Kayser, B. Helk, and B.L. Trout Predictive tools for stabilization of therapeutic proteins MAbs 1 2009 580 582
71. W. Wang Instability, stabilization, and formulation of liquid protein pharmaceuticals Int. J. Pharm. 185 1999 129 188 (Pubitemid 29392904)
72. W. Wang Protein aggregation and its inhibition in biopharmaceutics Int. J. Pharm. 289 2005 1 30 (Pubitemid 40093537)
73. W. Wang, S. Singh, D.L. Zeng, K. King, and S. Nema Antibody structure, instability, and formulation J. Pharm. Sci. 96 2007 1 26 (Pubitemid 46087335)