Leveraging SBDD in protein therapeutic development: Antibody engineering

Methods in Molecular Biology

Volumn 841, Issue , 2012, Pages 321-349

  Gilliland, Gary L ^a   Luo, Jinquan ^a   Vafa, Omid ^a   Almagro, Juan Carlos ^a  

^a CENTOCOR INC   (United States)

Author keywords

Affinity Maturation; Antibody Engineering; Antibody Humanization; Antibody Structure; Developability; Fc Effector Function.; Fc Engineering

Indexed keywords

ANTIBODY;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; HUMAN; PROTEIN ENGINEERING; X RAY CRYSTALLOGRAPHY;

ANTIBODIES; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN ENGINEERING;

EID: 84856483987     PISSN: 10643745     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-61779-520-6_14     Document Type: Article

References (144)

1. Reichert JM. (2008) Monoclonal antibodies as innovative therapeutics. Curr Pharm. Biotechnol . 9 , 423-430.
2. Aires da Silva F, Corte-Real S, Goncalves J. (2008) Recombinant antibodies as therapeutic agents: pathways for modeling new biodrugs. BioDrugs . 22 , 301-314.
3. Beck A, Wurch T, Bailly C, Corvaia N. (2010) Strategies and challenges for the next generation of therapeutic antibodies. Nat. Rev. Immunol . 10 , 345-352.
4. Kohler G, Milstein C. (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature . 256 , 495-497.
5. Smith GP. (1985) Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science . 228 , 1315-1317. (Pubitemid 15000355)
6. McCafferty J, Griffiths AD, Winter G, Chiswell DJ. (1990) Phage antibodies: filamentous phage displaying antibody variable domains. Nature . 348 , 552-554. (Pubitemid 120015109)
7. Marks JD, Hoogenboom HR, Bonnert TP, McCafferty J, Griffiths AD, Winter G. (1991) By-passing immunization. Human antibodies from V-gene libraries displayed on phage. J. Mol. Biol . 222 , 581-597.
8. Kelley B. (2009) Industrialization of mAb production technology: the bioprocessing industry at a crossroads. MAbs . 1 , 443-452.
9. Jefferis R. (2007) Antibody therapeutics: isotype and glycoform selection. Expert Opin. Biol. Ther . 7 , 1401-1413. (Pubitemid 47475656)
10. Presta LG. (2008) Molecular engineering and design of therapeutic antibodies. Curr. Opin. Immunol . 20 , 460-470.
11. Jefferis R. (2009) Recombinant antibody therapeutics: the impact of glycosylation on mechanisms of action. Trends Pharmacol. Sci . 30 , 356-362.
12. Holliger P, Hudson PJ. (2005) Engineered antibody fragments and the rise of single domains. Nat. Biotechnol . 23 , 1126-1136. (Pubitemid 41486394)
13. Skerra A. (2007) Alternative non-antibody scaffolds for molecular recognition. Curr Opin Biotechnol . 18 , 295-304. (Pubitemid 47385180)
14. Padlan EA. (1977) Structural basis for the specificity of antibody-antigen reactions and structural mechanisms for the diversification of antigen-binding specificities. Q. Rev. Biophys . 10 , 35-65. (Pubitemid 8065110)
15. Amzel LM, Poljak RJ. (1979) Threedimensional structure of immunoglobulins. Annu. Rev. Biochem . 48 , 961-997.
16. Davies DR, Metzger H. (1983) Structural basis of antibody function. Annu. Rev. Immunol . 1 , 87-117.
17. Wilson IA, Stanfield RL. (1994) Antibodyantigen interactions: new structures and new conformational changes. Curr. Opin. Struct. Biol . 4 , 857-867.
18. Stanfield RL, Wilson, I.A. Antibody Molecular Structure. In: An Z, ed. Therapeutic Monoclonal Antibodies: From Bench to Clinic: John Wiley & Sons, Inc.; 2010.
19. Porter RR. (1959) The hydrolysis of rabbit y-globulin and antibodies with crystalline papain. Biochem. J . 73 , 119-126.
20. Berman HM, Westbrook J, Feng Z, et al. (2000) The Protein Data Bank. Nucleic Acids Res . 28 , 235-242. (Pubitemid 30047768)
21. Schiffer M, Girling RL, Ely KR, Edmundson AB. (1973) Structure of a lambda-type Bence- Jones protein at 3.5-A resolution. Biochemistry . 12 , 4620-4631.
22. Poljak RJ, Amzel LM, Chen BL, Phizackerley RP, Saul F. (1974) The three-dimensional structure of the fab' fragment of a human myeloma immunoglobulin at 2.0-angstrom resolution. Proc. Natl. Acad. Sci. USA . 71 , 3440-3444.
23. Stanfield RL, Zemla A, Wilson IA, Rupp B. (2006) Antibody elbow angles are influenced by their light chain class. J. Mol. Biol . 357 , 1566-1574.
24. Lesk AM, Chothia C. (1988) Elbow motion in the immunoglobulins involves a molecular ball-and-socket joint. Nature . 335 , 188-190.
25. Wu TT, Kabat EA. (1970) An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J. Exp. Med . 132 , 211-250.
26. Kabat EA, Wu TT. (1971) Attempts to locate complementarity-determining residues in the variable positions of light and heavy chains. Ann. N Y Acad. Sci . 190 , 382-393.
27. Chothia C, Lesk AM. (1987) Canonical structures for the hypervariable regions of mmunoglobulins. J. Mol. Biol . 196 , 901-917. (Pubitemid 17127946)
28. Chothia C, Lesk AM, Tramontano A, et al. (1989) Conformations of immunoglobulin hypervariable regions. Nature . 342 , 877-883. (Pubitemid 20021331)
29. Chothia C, Lesk AM, Gherardi E, et al. (1992) Structural repertoire of the human VH segments. J. Mol. Biol . 227 , 799-817.
30. Tomlinson IM, Cox JP, Gherardi E, Lesk AM, Chothia C. (1995) The structural repertoire of the human V kappa domain. EMBO J . 14 , 4628-4638.
31. Vargas-Madrazo E, Lara-Ochoa F, Almagro JC. (1995) Canonical structure repertoire of the antigen-binding site of immunoglobulins suggests strong geometrical restrictions associated to the mechanism of immune recognition. J. Mol. Biol . 254 , 497-504. (Pubitemid 26001786)
32. Shirai H, Kidera A, Nakamura H. (1996) Structural classification of CDR-H3 in antibodies. FEBS Lett . 399 , 1-8. (Pubitemid 27007940)
33. Morea V, Tramontano A, Rustici M, Chothia C, Lesk AM. (1998) Conformations of the third hypervariable region in the VH domain of immunoglobulins. J Mol Biol . 275 , 269-294. (Pubitemid 28030004)
34. Collis AV, Brouwer AP, Martin AC. (2003) Analysis of the antigen combining site: correlations between length and sequence composition of the hypervariable loops and the nature of the antigen. J. Mol. Biol . 325 , 337-354. (Pubitemid 36062692)
35. Al-Lazikani B, Lesk AM, Chothia C. (1997) Standard conformations for the canonical structures of immunoglobulins. J. Mol. Biol . 273 , 927-948. (Pubitemid 27493729)
36. North B, Lehmann A, Dunbrack RL, Jr. (2010) A new clustering of antibody CDR loop conformations. J. Mol. Biol . 406 , 228-256.
37. Martin AC, Thornton JM. (1996) Structural families in loops of homologous proteins: automatic classification, modelling and application to antibodies. J. Mol. Biol . 263 , 800-815. (Pubitemid 26395069)
38. Sivasubramanian A, Sircar A, Chaudhury S, Gray JJ. (2009) Toward high-resolution homology modeling of antibody Fv regions and application to antibody-antigen docking. Proteins . 74 , 497-514.
39. Sircar A, Kim ET, Gray JJ. (2009) RosettaAntibody: antibody variable region homology modeling server. Nucleic Acids Res . 37 , W474-479.
40. Marcatili P, Rosi A, Tramontano A. (2008) PIGS: automatic prediction of antibody structures. Bioinformatics . 24 , 1953-1954.
41. Almagro JC, Beavers MP, Hernandez- Guzman F, Shaulsky J, Butenhof K, Maier J, Kelly K, Labute P, Thorsteinson N, Teplyakov A, Luo J, Sweet R, Gilliland GL (2011) Antibody Modeling Assessment. Proteins . 79, 3050-3066.
42. Marquart M, Deisenhofer J, Huber R, Palm W. (1980) Crystallographic refinement and atomic models of the intact immunoglobulin molecule Kol and its antigen-binding fragment at 3.0 A and 1.0 A resolution. J. Mol. Biol . 141 , 369-391. (Pubitemid 11227281)
43. Saphire EO, Stanfield RL, Crispin MD, et al . (2002) Contrasting IgG structures reveal extreme asymmetry and flexibility. J. Mol. Biol . 319 , 9-18. (Pubitemid 34729482)
44. Sondermann P, Huber R, Oosthuizen V, Jacob U. (2000) The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex. Nature . 406 , 267-273. (Pubitemid 30604397)
45. Deisenhofer J. (1981) Crystallographic refinement and atomic models of a human Fc fragment and its complex with fragment B of protein A from Staphylococcus aureus at 2.9- and 2.8-A resolution. Biochemistry . 20 , 2361-2370. (Pubitemid 11089772)
46. Matsumiya S, Yamaguchi Y, Saito J, et al . (2007) Structural comparison of fucosylated and nonfucosylated Fc fragments of human immunoglobulin G1. J. Mol. Biol . 368 , 767-779. (Pubitemid 46527615)
47. Jones PT, Dear PH, Foote J, Neuberger MS, Winter G. (1986) Replacing the complementarity- determining regions in a human antibody with those from a mouse. Nature . 321 , 522-525. (Pubitemid 16052256)
48. Reichert JM. (2010) Metrics for antibody therapeutics development. MAbs . 2 , 695-700.
49. Almagro JC, Strohl WR. Antibody Engineering: Humanization, Affinity Maturation and Selection Methods. In: An Z, ed. Therapeutic Monoclonal Antibodies: From Bench to Clinic: John Wiley & Sons, Inc.; 2009:302-327.
50. De Groot AS, Goldberg M, Moise L, Martin W. (2006) Evolutionary deimmunization: an ancillary mechanism for self-tolerance? Cell Immunol . 244 , 148-153. (Pubitemid 46738557)
51. Tamura M, Milenic DE, Iwahashi M, Padlan E, Schlom J, Kashmiri SV. (2000) Structural correlates of an anticarcinoma antibody: identification of specificity-determining residues (SDRs) and development of a minimally immunogenic antibody variant by retention of SDRs only. J. Immunol . 164 , 1432-1441. (Pubitemid 30067258)
52. Tan P, Mitchell DA, Buss TN, Holmes MA, Anasetti C, Foote J. (2002) "Superhumanized" antibodies: reduction of immunogenic potential by complementarity-determining region grafting with human germline sequences: application to an anti-CD28. J. Immunol . 169 , 1119-1125. (Pubitemid 34759912)
53. Lazar GA, Desjarlais JR, Jacinto J, Karki S, Hammond PW. (2007) A molecular immunology approach to antibody humanization and functional optimization. Mol. Immunol . 44 , 1986-1998.
54. Pelat T, Bedouelle H, Rees AR, Crennell SJ, Lefranc MP, Thullier P. (2008) Germline humanization of a non-human primate antibody that neutralizes the anthrax toxin, by in vitro and in silico engineering. J. Mol. Biol . 384 , 1400-1407.
55. Almagro JC, Fransson J. (2008) Humanization of antibodies. Front Biosci . 13 , 1619-1633. (Pubitemid 351611608)
56. Osbourn J, Groves M, Vaughan T. (2005) From rodent reagents to human therapeutics using antibody guided selection. Methods . 36 , 61-68. (Pubitemid 40558816)
57. Dall'Acqua WF, Damschroder MM, Zhang J, et al. (2005) Antibody humanization by framework shuffling. Methods . 36 , 43-60. (Pubitemid 40558815)
58. Padlan EA, Abergel C, Tipper JP. (1995) Identification of specificity-determining residues in antibodies. FASEB J . 9 , 133-139.
59. Matsuda F, Ishii K, Bourvagnet P, et al. (1998) The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus. J. Exp. Med . 188 , 2151-2162. (Pubitemid 28562531)
60. Schroeder HW, Jr., Cavacini L. (2010) Structure and function of immunoglobulins. J. Allergy Clin.. Immunol . 125 , S41-52.
61. Lefranc MP, Giudicelli V, Kaas Q, et al. (2005) IMGT, the international ImMunoGeneTics information system. Nucleic Acids Res . 33 , D593-597. (Pubitemid 40207943)
62. Queen C, Schneider WP, Selick HE, et al . (1989) A humanized antibody that binds to the interleukin 2 receptor. Proc. Natl. Acad. Sci. USA . 86 , 10029-10033. (Pubitemid 20030769)
63. Brezinschek HP, Foster SJ, Dorner T, Brezinschek RI, Lipsky PE. (1998) Pairing of variable heavy and variable kappa chains in individual naive and memory B cells. J. Immunol . 160 , 4762-4767. (Pubitemid 28215309)
64. de Wildt RM, Hoet RM, van Venrooij WJ, Tomlinson IM, Winter G. (1999) Analysis of heavy and light chain pairings indicates that receptor editing shapes the human antibody repertoire. J. Mol. Biol . 285 , 895-901. (Pubitemid 29054303)
65. Shi L, Wheeler JC, Sweet RW, et al. (2010) De novo selection of high-affinity antibodies from synthetic fab libraries displayed on phage as pIX fusion proteins. J. Mol. Biol . 397 , 385-396.
66. Fransson J, Teplyakov A, Raghunathan G, et al. (2010) Human framework adaptation of a mouse anti-human IL-13 antibody. J. Mol. Biol . 398 , 214-231.
67. Getts DR, Getts MT, McCarthy DP, Chastain EM, Miller SD. (2010) Have we overestimated the benefit of human(ized) antibodies? MAbs . 2 , 682-694.
68. Bernett MJ, Karki S, Moore GL, et al . (2010) Engineering fully human monoclonal antibodies from murine variable regions. J. Mol. Biol . 396 , 1474-1490.
69. Harding FA, Stickler MM, Razo J, DuBridge RB. (2010) The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. MAbs . 2 , 256-265.
70. Hwang WY, Almagro JC, Buss TN, Tan P, Foote J. (2005) Use of human germline genes in a CDR homology-based approach to antibody humanization. Methods . 36 , 35-42. (Pubitemid 40558814)
71. Hoet RM, Cohen EH, Kent RB, et al. (2005) Generation of high-affinity human antibodies by combining donor-derived and synthetic complementarity- determining-region diversity. Nat. Biotechnol . 23 , 344-348. (Pubitemid 41094423)
72. Rothe C, Urlinger S, Lohning C, et al. (2008) The human combinatorial antibody library HuCAL GOLD combines diversification of all six CDRs according to the natural immune system with a novel display method for efficient selection of high-affinity antibodies. J. Mol. Biol . 376 , 1182-1200.
73. Barbas CF, III, Hu D, Dunlop N, et al. (1994) In vitro evolution of a neutralizing human antibody to human immunodeficiency virus type 1 to enhance affinity and broaden strain cross-reactivity. Proc. Natl. Acad. Sci. USA . 91 , 3809-3813.
74. Hanes J, Jermutus L, Weber-Bornhauser S, Bosshard HR, Pluckthun A. (1998) Ribosome display efficiently selects and evolves highaffinity antibodies in vitro from immune libraries. Proc. Natl. Acad. Sci. USA . 95 , 14130-14135. (Pubitemid 28549332)
75. Midelfort KS, Hernandez HH, Lippow SM, Tidor B, Drennan CL, Wittrup KD. (2004) Substantial energetic improvement with minimal structural perturbation in a high affinity mutant antibody. J. Mol. Biol . 343 , 685-701. (Pubitemid 39311615)
76. Hawkins RE, Russell SJ, Winter G. (1992) Selection of phage antibodies by binding affinity. Mimicking affinity maturation. J. Mol. Biol . 226 , 889-896.
77. Hawkins RE, Russell SJ, Baier M, Winter G. (1993) The contribution of contact and noncontact residues of antibody in the affinity of binding to antigen. The interaction of mutant D1.3 antibodies with lysozyme. J. Mol. Biol . 234 , 958-964.
78. Lowman HB, Bass SH, Simpson N, Wells JA. (1991) Selecting high-affinity binding proteins by monovalent phage display. Biochemistry . 30 , 10832-10838.
79. Yang WP, Green K, Pinz-Sweeney S, Briones AT, Burton DR, Barbas CF, III. (1995) CDR walking mutagenesis for the affinity maturation of a potent human anti-HIV-1 antibody into the picomolar range. J. Mol. Biol . 254 , 392-403. (Pubitemid 26001779)
80. Bruhns P, Iannascoli B, England P, et al. (2009) Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses. Blood . 113 , 3716-3725.
81. Duncan AR, Woof JM, Partridge LJ, Burton DR, Winter G. (1988) Localization of the binding site for the human high-affinity Fc receptor on IgG. Nature . 332 , 563-564.
82. Alegre ML, Collins AM, Pulito VL, et al. (1992) Effect of a single amino acid mutation on the activating and immunosuppressive properties of a "humanized" OKT3 monoclonal antibody. J. Immunol . 148 , 3461-3468.
83. Shields RL, Namenuk AK, Hong K, et al. (2001) High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J. Biol. Chem . 276 , 6591-6604.
84. Bredius RG, Driedijk PC, Schouten MF, Weening RS, Out TA. (1992) Complement activation by polyclonal immunoglobulin G1 and G2 antibodies against Staphylococcus aureus, Haemophilus influenzae type b, and tetanus toxoid. Infect. Immun . 60 , 4838-4847.
85. Saeland E, Vidarsson G, Leusen JH, et al. (2003) Central role of complement in passive protection by human IgG1 and IgG2 antipneumococcal antibodies in mice. J. Immunol . 170 , 6158-6164. (Pubitemid 36682599)
86. Tawara T, Hasegawa K, Sugiura Y, et al. (2008) Complement activation plays a key role in antibody-induced infusion toxicity in monkeys and rats. J. Immunol . 180 , 2294-2298.
87. Armour KL, Clark MR, Hadley AG, Williamson LM. (1999) Recombinant human IgG molecules lacking Fcgamma receptor I binding and monocyte triggering activities. Eur. J. Immunol . 29, 2613-2624. (Pubitemid 29378132)
88. Armour KL, van de Winkel JG, Williamson LM, Clark MR. (2003) Differential binding to human FcgammaRIIa and FcgammaRIIb receptors by human IgG wildtype and mutant antibodies. Mol. Immunol . 40 , 585-593. (Pubitemid 37329917)
89. Lazar GA, Dang W, Karki S, et al . (2006) Engineered antibody Fc variants with enhanced effector function. Proc. Natl. Acad. Sci. USA . 103 , 4005-4010.
90. Tao MH, Morrison SL. (1989) Studies of aglycosylated chimeric mouse-human IgG. Role of carbohydrate in the structure and effector functions mediated by the human IgG constant region. J. Immunol . 143 , 2595-2601. (Pubitemid 19260070)
91. Raju TS. (2008) Terminal sugars of Fc glycans influence antibody effector functions of IgGs. Curr. Opin. Immunol . 20 , 471-478.
92. Moore GL, Chen H, Karki S, Lazar GA. (2010) Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions. MAbs . 2 , 320-328.
93. Labrijn AF, Aalberse RC, Schuurman J. (2008) When binding is enough: nonactivating antibody formats. Curr. Opin. Immunol . 20 , 479-485.
94. An Z, Forrest G, Moore R, et al. (2009) IgG2m4, an engineered antibody isotype with reduced Fc function. MAbs . 1 , 572-579.
95. Angal S, King DJ, Bodmer MW, et al. (1993) A single amino acid substitution abolishes the heterogeneity of chimeric mouse/human (IgG4) antibody. Mol. Immunol . 30 , 105-108. (Pubitemid 223036868)
96. Brambell FW, Hemmings WA, Morris IG. (1964) A Theoretical Model of Gamma-Globulin Catabolism. Nature . 203 , 1352-1354.
97. Roopenian DC, Akilesh S. (2007) FcRn: the neonatal Fc receptor comes of age. Nat. Rev. Immunol . 7 , 715-725. (Pubitemid 47327396)
98. Dall'Acqua WF, Woods RM, Ward ES, et al. (2002) Increasing the affinity of a human IgG1 for the neonatal Fc receptor: biological consequences. J. Immunol . 169 , 5171-5180. (Pubitemid 35217187)
99. Zalevsky J, Chamberlain AK, Horton HM, et al. (2010) Enhanced antibody half-life improves in vivo activity. Nat. Biotechnol . 28 , 157-159.
100. Qiao SW, Kobayashi K, Johansen FE, et al. (2008) Dependence of antibody-mediated presentation of antigen on FcRn. Proc. Natl. Acad. Sci. USA . 105 , 9337-9342.
101. Abel CA, Spiegelberg HL, Grey HM. (1968) The carbohydrate contents of fragments and polypeptide chains of human gamma-Gmyeloma proteins of different heavy-chain subclasses. Biochemistry . 7 , 1271-1278.
102. Spiegelberg HL, Abel CA, Fishkin BG, Grey HM. (1970) Localization of the carbohydrate within the variable region of light and heavy chains of human gamma g myeloma proteins. Biochemistry . 9 , 4217-4223.
103. Wright A, Morrison SL. (1993) Antibody variable region glycosylation: biochemical and clinical effects. Springer Semin. Immunopathol . 15 , 259-273. (Pubitemid 23281032)
104. Co MS, Scheinberg DA, Avdalovic NM, et al. (1993) Genetically engineered deglycosylation of the variable domain increases the affinity of an anti-CD33 monoclonal antibody. Mol. Immunol . 30 , 1361-1367.
105. Khurana S, Raghunathan V, Salunke DM. (1997) The variable domain glycosylation in a monoclonal antibody specific to GnRH modulates antigen binding. Biochem. Biophys. Res. Commun . 234 , 465-469. (Pubitemid 27243926)
106. Leibiger H, Wustner D, Stigler RD, Marx U. (1999) Variable domain-linked oligosaccharides of a human monoclonal IgG: structure and influence on antigen binding. Biochem. J . 338 ( Pt 2), 529-538.
107. Wallick SC, Kabat EA, Morrison SL. (1988) Glycosylation of a VH residue of a monoclonal antibody against alpha (1-6) dextran increases its affinity for antigen. J. Exp. Med . 168 , 1099-1109.
108. Wright A, Tao MH, Kabat EA, Morrison SL. (1991) Antibody variable region glycosylation: position effects on antigen binding and carbohydrate structure. EMBO J . 10 , 2717-2723. (Pubitemid 21905287)
109. Coloma MJ, Trinh RK, Martinez AR, Morrison SL. (1999) Position effects of variable region carbohydrate on the affinity and in vivo behavior of an anti-(1->6) dextran antibody. J. Immunol . 162 , 2162-2170. (Pubitemid 29288838)
110. Rudd PM, Wormald MR, Harvey DJ, et al. (1999) Oligosaccharide analysis and molecular modeling of soluble forms of glycoproteins belonging to the Ly-6, scavenger receptor, and immunoglobulin superfamilies expressed in Chinese hamster ovary cells. Glycobiology . 9 , 443-458. (Pubitemid 29240342)
111. Qian J, Liu T, Yang L, Daus A, Crowley R, Zhou Q. (2007) Structural characterization of N-linked oligosaccharides on monoclonal antibody cetuximab by the combination of orthogonal matrix-assisted laser desorption/ ionization hybrid quadrupole-quadrupole time-of-flight tandem mass spectrometry and sequential enzymatic digestion. Anal. Biochem . 364 , 8-18. (Pubitemid 46497948)
112. Imclone Systems, Inc Biologic License Application 125084, Erbitux (Cetuximab). In; 2004.
113. Frazer J, Capra J. Fundamental immunology. In: Immunoglobulins: Structure and function. 4th ed: Lippincott-Raven; 1999:37-74.
114. Wang W, Singh S, Zeng DL, King K, Nema S. (2007) Antibody structure, instability, and formulation. J. Pharm. Sci . 96 , 1-26. (Pubitemid 46087335)
115. Robinson N. (2002) Protein deamidation. Proc. Natl. Acad. Sci. USA . 99 , 5283-5288. (Pubitemid 34411540)
116. Geiger T, Clarke S. (1987) Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides. Succinimidelinked reactions that contribute to protein degradation. J. Biol. Chem . 262 , 785-794. (Pubitemid 17005254)
117. Clarke S. (1987) Propensity for spontaneous succinimide formation from aspartyl and asparaginyl residues in cellular proteins. Int. J. Pept. Protein Res . 30 , 808-821.
118. Robinson NE RZ, Robinson BR, Robinson AL, Robinson JA, Robinson ML, Robinson AB. (2004) Structure-dependent nonenzymatic deamidation of glutaminyl and asparaginyl pentapeptides. J. Peptide Res . 63 , 426-436. (Pubitemid 38703633)
119. Ji JA, Zhang B, Cheng W, Wang YJ. (2009) Methionine, tryptophan, and histidine oxidation in a model protein, PTH: mechanisms and stabilization. J. Pharm. Sci . 98 , 4485-4500.
120. Pan H, Chen K, Chu L, Kinderman F, Apostol I, Huang G. (2009) Methionine oxidation in human IgG2 Fc decreases binding affinities to protein A and FcRn. Protein Sci . 18 , 424-433.
121. Tomlinson IM, Walter G, Marks JD, Llewelyn MB, Winter G. (1992) The repertoire of human germline VH sequences reveals about fifty groups of VH segments with different hypervariable loops. J. Mol. Biol . 227 , 776-798.
122. Remmele RL, Gombotz WR. (2000) Differential scanning calorimetry: A practical tool for elucidating stability of liquid biopharmaceuticals. Biopharm. 13 , 36-46.
123. Garber E, Demarest SJ. (2007) A broad range of Fab stabilities within a host of therapeutic IgGs. Biochem Biophys. Res. Commun . 355 , 751-757. (Pubitemid 46343718)
124. Pepinsky RB, Silvian L, Berkowitz SA, et al. (2010) Improving the solubility of anti- LINGO-1 monoclonal antibody Li33 by isotype switching and targeted mutagenesis. Protein Science . 19 , 954-966.
125. Ewert S, Honegger A, Pluckthun A. (2004) Stability improvement of antibodies for extracellular and intracellular applications: CDR grafting to stable frameworks and structurebased framework engineering. Methods . 34 , 184-199. (Pubitemid 39092813)
126. Ewert S, Huber T, Honegger A, Pluckthun A. (2003) Biophysical properties of human antibody variable domains. J. Mol. Biol . 325 , 531-553. (Pubitemid 36062681)
127. Worn A, Pluckthun A. (1998) Mutual stabilization of VL and VH in single-chain antibody fragments, investigated with mutants engineered for stability. Biochemistry . 37 , 13120-13127. (Pubitemid 28449555)
128. Spada S, Honegger A, Pluckthun A. (1998) Reproducing the natural evolution of protein structural features with the selectively infective phage (SIP) technology. The kink in the first strand of antibody kappa domains. J. Mol. Biol . 283 , 395-407. (Pubitemid 28470417)
129. Worn A, Pluckthun A. (2001) Stability engineering of antibody single-chain Fv fragments. J. Mol. Biol . 305 , 989-1010. (Pubitemid 33028934)
130. Glockshuber R, Malia M, Pfitzinger I, Pluckthun A. (1990) A comparison of strategies to stabilize immunoglobulin Fv-fragments. Biochemistry . 29 , 1362-1367. (Pubitemid 20063361)
131. Forrer P, Jung S, Pluckthun A. (1999) Beyond binding: using phage display to select for structure, folding and enzymatic activity in proteins. Curr. Opin. Struct. Biol . 9 , 514-520. (Pubitemid 29377897)
132. Luo J, Obmolova G, Huang A, et al. (2010) Coevolution of antibody stability and Vkappa CDR-L3 canonical structure. J. Mol. Biol . 402 , 708-719.
133. Wiens GD, Roberts VA, Whitcomb EA, O'Hare T, Stenzel-Poore MP, Rittenberg MB. (1998) Harmful somatic mutations: lessons from the dark side. Immunol. Rev . 162 , 197-209. (Pubitemid 28182136)
134. Wang W, Nema S, Teagarden D. (2010) Protein aggregation-pathways and influencing factors. Int. J. Pharm . 390 , 89-99.
135. Trevino SR, Scholtz, J. M., Pace, C. N. (2008) Measuring and Increasing Protein Solubility. Journal of Pharmaceutical Sciences . 97 , 4155-4166.
136. Chennamsetty N, Helk B, Voynov V, Kayser V, Trout BL. (2009) Aggregation-prone motifs in human immunoglobulin G. J. Mol. Biol . 391 , 404-413.
137. Chennamsetty N, Voynov V, Kayser V, Helk B, Trout BL. (2009) Design of therapeutic proteins with enhanced stability. Proc. Natl. Acad. Sci. USA . 106 , 11937-11942.
138. Chennamsetty N, Voynov V, Kayser V, Helk B, Trout BL. (2010) Prediction of aggregation prone regions of therapeutic proteins. J. Phys. Chem. B . 114 , 6614-6624.
139. Wang X, Singh SK, Kumar S. (2010) Potential aggregation-prone regions in complementarity- determining regions of antibodies and their contribution towards antigen recognition: a computational analysis. Pharm. Res . 27 , 1512-1529.
140. Wang X, Das TK, Singh SK, Kumar S. (2009) Potential aggregation prone regions in biotherapeutics: A survey of commercial monoclonal antibodies. MAbs . 1 , 254-267.
141. Wu S-J, Luo J, O'Neil KT, Kang J, Lacy ER, Canziani G, Baker A, Huang M, Tang Q, Raju TS, Jacobs SA, Teplyakov A, Gilliland G, Feng Y. (2010) Structure-based engineering of a monoclonal antibody for improved solubility. Pro. Eng. Des. Sel . 23, 643-651.
142. Teplyakov A, Obmolova G, Wu SJ, et al. (2009) Epitope mapping of anti-interleukin-13 neutralizing antibody CNTO607. J. Mol. Biol . 389 , 115-123.
143. Harris LJ, Larson SB, Hasel KW, Day J, Greenwood A, McPherson A. (1992) The three-dimensional structure of an intact monoclonal antibody for canine lymphoma. Nature . 360 , 369-372. (Pubitemid 23000680)
144. Bhat TN, Bentley GA, Boulot G, et al. (1994) Bound water molecules and conformational stabilization help mediate an antigen-antibody association. Proc. Natl. Acad. Sci. USA . 91 , 1089-1093. (Pubitemid 24048514)