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Formulation and Delivery Issues for Monoclonal Antibody Therapeutics

  • Ann L. Daugherty
  • Randall J. Mrsny
Chapter
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume XI)

Abstract

Therapeutic and diagnostic antibodies have become the fastest growing area of biopharmaceutical applications. There are now 18 monoclonal antibodies on the market and over 100 in clinical trials, which highlights the significance of these therapeutics and the advances made in antibody engineering. Further, by 2008, engineered antibodies are projected to be the source of over a third of the revenues from biotechnology (Baker 2005; Reichert et al. 2005).

A few seminal events that have led to the current and projected prominence of antibodies as biopharmaceuticals include the identification of methods to generate murine monoclonal versions of antibodies (Kohler and Milstein 1975), the cloning of human antibody sequences to allow for humanization of murine monoclonal antibodies through complementary-determining region (CDR) grafting (Jones et al. 1986), and even the establishment of fully humanized systems to generate monoclonal antibodies (Peterson 2005). With the sequential identification of these technological advances, antibodies for therapeutic and prophylactic indications have moved from fully murine, to partially murine (mostly human), and to completely human constructions. Added to these events, dramatic advances in production have led to the ability to prepare monoclonal antibodies at scales that can provide sufficient material at costs that make this area appealing to pharmaceutical companies. One important outcome of these various advances is a greater potential to use antibody drugs in chronic settings, tremendously expanding their biopharmaceutical applications.

Keywords

Antibody Formulation PLGA Microsphere Gemtuzumab Ozogamicin Methionine Sulfoxide Antibody Drug 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments:

The authors wish to thank Reed Harris, Tom Patapoff, and Nancy Valente for their very insightful conversations and helpful suggestions. The review of the manuscript by Xanthe Lam, Brian Lobo, and Chung Hsu is appreciated. The references cited in this review were not intended to be inclusive of all of the seminal publications in the ever-expanding area of antibody stability and formulation. The relatively small numbers of references cited were selected to highlight specific aspects within the scope of this review. We regret that we could not cite many excellent publications that have made important contributions to this field.

References

  1. Adams GP, Weiner LM (2005) Monoclonal antibody therapy of cancer. Nat Biotechnol 23(9):1147–1157PubMedGoogle Scholar
  2. Al-Abdulla I et al (2003) Formulation of a liquid ovine Fab-based antivenom for the treatment of envenomation by the Nigerian carpet viper (Echis ocellatus). Toxicon 42(4):399–404PubMedGoogle Scholar
  3. Andya JD et al (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(3):350–358PubMedGoogle Scholar
  4. Andya JD, Hsu CC, Shire SJ (2003) Mechanisms of aggregate formation and carbohydrate excipient stabilization of lyophilized humanized monoclonal antibody formulations. AAPS PharmSci 5(2):E10Google Scholar
  5. Arakawa T, Kita Y, Carpenter JF (1991) Protein–solvent interactions in pharmaceutical formulations. Pharm Res 8(3):285–291PubMedGoogle Scholar
  6. Atkinson EM, Klum W (2001) Formulations strategies for biopharmaceuticals – ensuring success to market. IDrugs 4(5):557–560PubMedGoogle Scholar
  7. Baert F et al (2003) Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med 348(7):601–608PubMedGoogle Scholar
  8. Baker M (2005) Upping the ante on antibodies. Nat Biotechnol 23(9):1065–1072PubMedGoogle Scholar
  9. Balthasar S et al (2005) Preparation and characterisation of antibody modified gelatin nanoparticles as drug carrier system for uptake in lymphocytes. Biomaterials 26(15):2723–2732PubMedGoogle Scholar
  10. Baynes BM, Trout BL (2004) Rational design of solution additives for the prevention of protein aggregation. Biophys J 87(3):1631–1639PubMedGoogle Scholar
  11. Bazin R et al (1994) Use of hu-IgG-SCID mice to evaluate the in vivo stability of human monoclonal IgG antibodies. J Immunol Methods 172(2):209–217PubMedGoogle Scholar
  12. Bitonti AJ et al (2004) Pulmonary delivery of an erythropoietin Fc fusion protein in non-human primates through an immunoglobulin transport pathway. Proc Natl Acad Sci U S A 101(26):9763–9768PubMedGoogle Scholar
  13. Bogard WC Jr et al (1989) Practical considerations in the production, purification, and formulation of monoclonal antibodies for immunoscintigraphy and immunotherapy. Semin Nucl Med 19(3):202–220PubMedGoogle Scholar
  14. Brannon-Peppas L, Blanchette JO (2004) Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 56(11):1649–1659PubMedGoogle Scholar
  15. Breen ED et al (2001) Effect of moisture on the stability of a lyophilized humanized monoclonal antibody formulation. Pharm Res 18(9):1345–1353PubMedGoogle Scholar
  16. Chang LL et al (2005) Effect of sorbitol and residual moisture on the stability of lyophilized antibodies: implications for the mechanism of protein stabilization in the solid state. J Pharm Sci 94(7):1445–1455PubMedGoogle Scholar
  17. Chapman SA et al (2004) Acute renal failure and intravenous immune globulin: occurs with sucrose-stabilized, but not with d-sorbitol-stabilized, formulation. Ann Pharmacother 38(12):2059–2067PubMedGoogle Scholar
  18. Chatenoud L (2003) CD3-specific antibody-induced active tolerance: from bench to bedside. Nat Rev Immunol 3(2):123–132PubMedGoogle Scholar
  19. Cheifetz A, Mayer L (2005) Monoclonal antibodies, immunogenicity, and associated infusion reactions. Mt Sinai J Med 72(4):250–256PubMedGoogle Scholar
  20. Cheifetz A et al (2003) The incidence and management of infusion reactions to infliximab: a large center experience. Am J Gastroenterol 98(6):1315–1324PubMedGoogle Scholar
  21. Chelius D, Rehder DS, Bondarenko PV (2005) Identification and characterization of deamidation sites in the conserved regions of human immunoglobulin gamma antibodies. Anal Chem 77(18):6004–6011PubMedGoogle Scholar
  22. Cleland JL, Powell MF, Shire SJ (1993) The development of stable protein formulations: a close look at protein aggregation, deamidation, and oxidation. Crit Rev Ther Drug Carrier Syst 10(4):307–377PubMedGoogle Scholar
  23. Cleland JL et al (2001) A specific molar ratio of stabilizer to protein is required for storage stability of a lyophilized monoclonal antibody. J Pharm Sci 90(3):310–321PubMedGoogle Scholar
  24. Cook-Bruns N (2001) Retrospective analysis of the safety of Herceptin immunotherapy in metastatic breast cancer. Oncology 61(Suppl 2):58–66PubMedGoogle Scholar
  25. Cordoba AJ et al (2005) Non-enzymatic hinge region fragmentation of antibodies in solution. J Chromatogr B Analyt Technol Biomed Life Sci 818(2):115–121PubMedGoogle Scholar
  26. Corthesy B (2003) Recombinant secretory immunoglobulin A in passive immunotherapy: linking immunology and biotechnology. Curr Pharm Biotechnol 4(1):51–67PubMedGoogle Scholar
  27. Costantino HR et al (1998a) Effect of excipients on the stability and structure of lyophilized recombinant human growth hormone. J Pharm Sci 87(11):1412–1420PubMedGoogle Scholar
  28. Costantino HR et al (1998b) Effect of mannitol crystallization on the stability and aerosol performance of a spray-dried pharmaceutical protein, recombinant humanized anti-IgE monoclonal antibody. J Pharm Sci 87(11):1406–1411PubMedGoogle Scholar
  29. Crandall WV, Mackner LM (2003) Infusion reactions to infliximab in children and adolescents: frequency, outcome and a predictive model. Aliment Pharmacol Ther 17(1):75–84PubMedGoogle Scholar
  30. Daugherty AL et al (1997) Pharmacological modulation of the tissue response to implanted polylactic-co-glycolic acid microspheres. Eur J Pharmacol Biopharm 44(1637):89–102Google Scholar
  31. Demarest SJ, Rogers J, Hansen G (2004) Optimization of the antibody C(H)3 domain by residue frequency analysis of IgG sequences. J Mol Biol 335(1):41–48PubMedGoogle Scholar
  32. Dinauer N et al (2005) Selective targeting of antibody-conjugated nanoparticles to leukemic cells and primary T-lymphocytes. Biomaterials 26(29):5898–5906PubMedGoogle Scholar
  33. Duddu SP, Dal Monte PR (1997) Effect of glass transition temperature on the stability of lyophilized formulations containing a chimeric therapeutic monoclonal antibody. Pharm Res 14(5):591–595PubMedGoogle Scholar
  34. Dyba M, Tarasova NI, Michejda CJ (2004) Small molecule toxins targeting tumor receptors. Curr Pharm Des 10(19):2311–2334PubMedGoogle Scholar
  35. Edwards DA et al (1997) Large porous particles for pulmonary drug delivery. Science 276(5320):1868–1871PubMedGoogle Scholar
  36. Ewert S, Honegger A, Pluckthun A (2004) Stability improvement of antibodies for extracellular and intracellular applications: CDR grafting to stable frameworks and structure-based framework engineering. Methods 34(2):184–199PubMedGoogle Scholar
  37. Ferro-Flores G, Lezama-Carrasco J (1994) A freeze dried kit formulation for the preparation of 99mTc-EHDP-MoAb-IOR CEA1 complex. Nucl Med Biol 21(7):1013–1016PubMedGoogle Scholar
  38. Friedli HR (1987) Methodology and safety considerations in the production of an intravenous immunoglobulin preparation. Pharmacotherapy 7(2):S36–S40Google Scholar
  39. Gekko K (1981) Mechanism of polyol-induced protein stabilization: solubility of amino acids and diglycine in aqueous polyol solutions. J Biochem 90(6):1633–1641PubMedGoogle Scholar
  40. Grainger DW (2004) Controlled-release and local delivery of therapeutic antibodies. Expert Opin Biol Ther 4(7):1029–1044PubMedGoogle Scholar
  41. Granholm AC et al (1998) A non-invasive system for delivering neural growth factors across the blood–brain barrier: a review. Rev Neurosci 9(1):31–55PubMedGoogle Scholar
  42. Griffiths HR (2000) Antioxidants and protein oxidation. Free Radic Res 33(Suppl):S47–S58Google Scholar
  43. Gupta S, Kaisheva E (2003) Development of a multidose formulation for a humanized monoclonal antibody using experimental design techniques. AAPS PharmSci 5(2):E8Google Scholar
  44. Gupta RK, Chang AC, Siber GR (1998) Biodegradable polymer microspheres as vaccine adjuvants and delivery systems. Dev Biol Stand 92:63–78PubMedGoogle Scholar
  45. Hall CG, Abraham GN (1984) Reversible self-association of a human myeloma protein. Thermodynamics and relevance to viscosity effects and solubility. Biochemistry 23(22):5123–5129PubMedGoogle Scholar
  46. Harris RJ (2005) Heterogeneity of recombinant antibodies: linking structure to function. Dev Biol (Basel) 122:117–127Google Scholar
  47. Harris RJ et al (2001) Identification of multiple sources of charge heterogeneity in a recombinant antibody. J Chromatogr B Biomed Sci Appl 752(2):233–245PubMedGoogle Scholar
  48. Hasegawa G et al (2005) Synthesis and characterization of a novel reagent containing dansyl group, which specifically alkylates sulfhydryl group: an example of application for protein chemistry. J Biochem Biophys Methods 63(1):33–42PubMedGoogle Scholar
  49. Heinis C, Alessi P, Neri D (2004) Engineering a thermostable human prolyl endopeptidase for antibody-directed enzyme prodrug therapy. Biochemistry 43(20):6293–6303PubMedGoogle Scholar
  50. Hodoniczky J, Zheng YZ, James DC (2005) Control of recombinant monoclonal antibody effector functions by fc N-glycan remodeling in vitro. Biotechnol Prog 21(6):1644–1652PubMedGoogle Scholar
  51. Holliger P, Hudson PJ (2005) Engineered antibody fragments and the rise of single domains. Nat Biotechnol 23(9):1126–1136PubMedGoogle Scholar
  52. Horie K et al (2004) Suppressive effect of functional drinking yogurt containing specific egg yolk immunoglobulin on Helicobacter pylori in humans. J Dairy Sci 87(12):4073–4079PubMedGoogle Scholar
  53. Hsu CC et al (1992) Determining the optimum residual moisture in lyophilized protein pharmaceuticals. Dev Biol Stand 74:255–270 discussion 271PubMedGoogle Scholar
  54. Hsu CC et al (1996) Design and application of a low-temperature Peltier-cooling microscope stage. J Pharm Sci 85(1):70–74PubMedGoogle Scholar
  55. Huang L et al (2005) In vivo deamidation characterization of monoclonal antibody by LC/MS/MS. Anal Chem 77(5):1432–1439PubMedGoogle Scholar
  56. Idusogie EE et al (2001) Engineered antibodies with increased activity to recruit complement. J Immunol 166(4):2571–2575PubMedGoogle Scholar
  57. Imai M et al (2005) Complement-mediated mechanisms in anti-GD2 monoclonal antibody therapy of murine metastatic cancer. Cancer Res 65(22):10562–10568PubMedGoogle Scholar
  58. Jasin HE (1993) Oxidative modification of inflammatory synovial fluid immunoglobulin G. Inflammation 17(2):167–181PubMedGoogle Scholar
  59. Javed Q et al (2002) Tumor necrosis factor-alpha antibody eluting stents reduce vascular smooth muscle cell proliferation in saphenous vein organ culture. Exp Mol Pathol 73(2):104–111PubMedGoogle Scholar
  60. Jefferis R (2005) Glycosylation of recombinant antibody therapeutics. Biotechnol Prog 21(1):11–16PubMedGoogle Scholar
  61. Jespers L et al (2004) Crystal structure of HEL4, a soluble, refoldable human V(H) single domain with a germ-line scaffold. J Mol Biol 337(4):893–903PubMedGoogle Scholar
  62. Jones PT et al (1986) Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 321(6069):522–525PubMedGoogle Scholar
  63. Jones AJ et al (1997) Recombinant human growth hormone poly(lactic-co-glycolic acid) microsphere formulation development. Adv Drug Deliv Rev 28(1):71–84PubMedGoogle Scholar
  64. Kawade Y (1985) Neutralization of activity of effector protein by monoclonal antibody: formulation of antibody dose-dependence of neutralization for an equilibrium system of antibody, effector, and its cellular receptor. Immunology 56(3):497–504PubMedGoogle Scholar
  65. Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256(5517):495–497PubMedGoogle Scholar
  66. Kroon DJ, Baldwin-Ferro A, Lalan P (1992) Identification of sites of degradation in a therapeutic monoclonal antibody by peptide mapping. Pharm Res 9(11):1386–1393PubMedGoogle Scholar
  67. Kuo PY, Sherwood JK, Saltzman WM (1998) Topical antibody delivery systems produce sustained levels in mucosal tissue and blood. Nat Biotechnol 16(2):163–167PubMedGoogle Scholar
  68. Lackey CA et al (2002) A biomimetic pH-responsive polymer directs endosomal release and intracellular delivery of an endocytosed antibody complex. Bioconjug Chem 13(5):996–1001PubMedGoogle Scholar
  69. Lam XM, Yang JY, Cleland JL (1997) Antioxidants for prevention of methionine oxidation in recombinant monoclonal antibody HER2. J Pharm Sci 86(11):1250–1255PubMedGoogle Scholar
  70. Lavelle EC et al (1999) The stability and immunogenicity of a protein antigen encapsulated in biodegradable microparticles based on blends of lactide polymers and polyethylene glycol. Vaccine 17(6):512–529PubMedGoogle Scholar
  71. Lencer WI, Blumberg RS (2005) A passionate kiss, then run: exocytosis and recycling of IgG by FcRn. Trends Cell Biol 15(1):5–9PubMedGoogle Scholar
  72. Lonberg N (2005) Human antibodies from transgenic animals. Nat Biotechnol 23(9):1117–1125PubMedGoogle Scholar
  73. Luzardo-Alvarez A et al (2005) Biodegradable microspheres alone do not stimulate murine macrophages in vitro, but prolong antigen presentation by macrophages in vitro and stimulate a solid immune response in mice. J Control Release 109(1–3):62–76PubMedGoogle Scholar
  74. Ma JK et al (1998) Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nat Med 4(5):601–606PubMedGoogle Scholar
  75. Ma X et al (2001) Characterization of murine monoclonal antibody to tumor necrosis factor (TNF-MAb) formulation for freeze-drying cycle development. Pharm Res 18(2):196–202PubMedGoogle Scholar
  76. Mahler HC et al (2005) Induction and analysis of aggregates in a liquid IgG1-antibody formulation. Eur J Pharm Biopharm 59(3):407–417PubMedGoogle Scholar
  77. Merluzzi S et al (2000) Humanized antibodies as potential drugs for therapeutic use. Adv Clin Path 4(2):77–85PubMedGoogle Scholar
  78. Middaugh CR et al (1978) Physicochemical characterization of six monoclonal cryoimmunoglobulins: possible basis for cold-dependent insolubility. Proc Natl Acad Sci U S A 75(7):3440–3444PubMedGoogle Scholar
  79. Mimura Y et al (1995) Microheterogeneity of mouse antidextran monoclonal antibodies. Electrophoresis 16(1):116–123PubMedGoogle Scholar
  80. Mine Y, Kovacs-Nolan J (2002) Chicken egg yolk antibodies as therapeutics in enteric infectious disease: a review. J Med Food 5(3):159–169PubMedGoogle Scholar
  81. Mire-Sluis AR (2001) Progress in the use of biological assays during the development of biotechnology products. Pharm Res 18(9):1239–1246PubMedGoogle Scholar
  82. Moore JM, Patapoff TW, Cromwell ME (1999) Kinetics and thermodynamics of dimer formation and dissociation for a recombinant humanized monoclonal antibody to vascular endothelial growth factor. Biochemistry 38(42):13960–13967PubMedGoogle Scholar
  83. Mordenti J et al (1999) Intraocular pharmacokinetics and safety of a humanized monoclonal antibody in rabbits after intravitreal administration of a solution or a PLGA microsphere formulation. Toxicol Sci 52(1):101–106PubMedGoogle Scholar
  84. Morgan PE, Sturgess AD, Davies MJ (2005) Increased levels of serum protein oxidation and correlation with disease activity in systemic lupus erythematosus. Arthritis Rheum 52(7):2069–2079PubMedGoogle Scholar
  85. Mueller BM, Wrasidlo WA, Reisfeld RA (1990) Antibody conjugates with morpholinodoxorubicin and acid-cleavable linkers. Bioconjug Chem 1(5):325–330PubMedGoogle Scholar
  86. Nakamura T et al (2004) Antibody-targeted cell fusion. Nat Biotechnol 22(3):331–336PubMedGoogle Scholar
  87. O’Hagan DT et al (1991) Biodegradable microparticles as controlled release antigen delivery systems. Immunology 73(2):239–242PubMedGoogle Scholar
  88. Page M et al (1995) Fragmentation of therapeutic human immunoglobulin preparations. Vox Sang 69(3):183–194PubMedGoogle Scholar
  89. Panka DJ (1997) Glycosylation is influential in murine IgG3 self-association. Mol Immunol 34(8–9):593–598PubMedGoogle Scholar
  90. Park JW et al (1995) Development of anti-p185HER2 immunoliposomes for cancer therapy. Proc Natl Acad Sci U S A 92(5):1327–1331PubMedGoogle Scholar
  91. Park JW, Benz CC, Martin FJ (2004) Future directions of liposome- and immunoliposome-based cancer therapeutics. Semin Oncol 31(6 Suppl 13):196–205PubMedGoogle Scholar
  92. Peterson NC (2005) Advances in monoclonal antibody technology: genetic engineering of mice, cells, and immunoglobulins. ILAR J 46(3):314–319PubMedGoogle Scholar
  93. Poelstra KA et al (2002) Prophylactic treatment of gram-positive and gram-negative abdominal implant infections using locally delivered polyclonal antibodies. J Biomed Mater Res 60(1):206–215PubMedGoogle Scholar
  94. Presta LG (2002) Engineering antibodies for therapy. Curr Pharm Biotechnol 3(3):237–256PubMedGoogle Scholar
  95. Radkiewicz JL et al (2001) Neighboring side chain effects on asparaginyl and aspartyl degradation: an ab initio study of the relationship between peptide conformation and backbone NH acidity. J Am Chem Soc 123(15):3499–3506PubMedGoogle Scholar
  96. Reichert JM et al (2005) Monoclonal antibody successes in the clinic. Nat Biotechnol 23(9):1073–1078PubMedGoogle Scholar
  97. Reilly RM, Domingo R, Sandhu J (1997) Oral delivery of antibodies. Future pharmacokinetic trends. Clin Pharmacokinet 32(4):313–323PubMedGoogle Scholar
  98. Riggin A et al (1991) Solution stability of the monoclonal antibody-vinca alkaloid conjugate, KS1/4-DAVLB. Pharm Res 8(10):1264–1269PubMedGoogle Scholar
  99. Robinson NE, Robinson AB (2001a) Prediction of protein deamidation rates from primary and three-dimensional structure. Proc Natl Acad Sci U S A 98(8):4367–4372PubMedGoogle Scholar
  100. Robinson NE, Robinson AB (2001b) Deamidation of human proteins. Proc Natl Acad Sci U S A 98(22):12409–12413PubMedGoogle Scholar
  101. Robinson NE, Robinson AB (2001c) Molecular clocks. Proc Natl Acad Sci U S A 98(3):944–949PubMedGoogle Scholar
  102. Robinson NE, Robinson AB (2004) Prediction of primary structure deamidation rates of asparaginyl and glutaminyl peptides through steric and catalytic effects. J Pept Res 63(5):437–448PubMedGoogle Scholar
  103. Robinson AB, McKerrow JH, Cary P (1970) Controlled deamidation of peptides and proteins: an experimental hazard and a possible biological timer. Proc Natl Acad Sci U S A 66(3):753–757PubMedGoogle Scholar
  104. Robinson NE et al (2004) Structure-dependent nonenzymatic deamidation of glutaminyl and asparaginyl pentapeptides. J Pept Res 63(5):426–436PubMedGoogle Scholar
  105. Rojas IA, Slunt JB, Grainger DW (2000) Polyurethane coatings release bioactive antibodies to reduce bacterial adhesion. J Control Release 63(1–2):175–189PubMedGoogle Scholar
  106. Rudikoff S et al (1982) Single amino acid substitution altering antigen-binding specificity. Proc Natl Acad Sci U S A 79(6):1979–1983PubMedGoogle Scholar
  107. Saito G, Swanson JA, Lee KD (2003) Drug delivery strategy utilizing conjugation via reversible disulfide linkages: role and site of cellular reducing activities. Adv Drug Deliv Rev 55(2):199–215PubMedGoogle Scholar
  108. Saltzman WM et al (2000) Long-term vaginal antibody delivery: delivery systems and biodistribution. Biotechnol Bioeng 67(3):253–264PubMedGoogle Scholar
  109. Sane SU, Wong R, Hsu CC (2004) Raman spectroscopic characterization of drying-induced structural changes in a therapeutic antibody: correlating structural changes with long-term stability. J Pharm Sci 93(4):1005–1018PubMedGoogle Scholar
  110. Sarciaux JM et al (1999) Effects of buffer composition and processing conditions on aggregation of bovine IgG during freeze-drying. J Pharm Sci 88(12):1354–1361PubMedGoogle Scholar
  111. Schnyder A, Huwyler J (2005) Drug transport to brain with targeted liposomes. NeuroRx 2(1):99–107PubMedGoogle Scholar
  112. Sgouris JT (1970) Studies on immune serum globulin (IgG) and its modification for intravenous administration. Prog Immunobiol Stand 4:104–113PubMedGoogle Scholar
  113. Shen FJ et al (1996) The application of tert-butylhydroperoxide oxidation to study sites of potential methionine oxidation in a recombinant antibody. In: Marshak D (ed) Techniques in protein chemistry VII. Academic, San Diego, pp 275–284Google Scholar
  114. Shields RL 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(9):6591–6604PubMedGoogle Scholar
  115. Siberil S et al (2005) Selection of a human anti-RhD monoclonal antibody for therapeutic use: impact of IgG glycosylation on activating and inhibitory Fc gamma R functions. Clin Immunol 118(2–3):170–179PubMedGoogle Scholar
  116. Spiekermann GM et al (2002) Receptor-mediated immunoglobulin G transport across mucosal barriers in adult life: functional expression of FcRn in the mammalian lung. J Exp Med 196(3):303–310PubMedGoogle Scholar
  117. Stockwin LH, Holmes S (2003) Antibodies as therapeutic agents: vive la renaissance!. Expert Opin Biol Ther 3(7):1133–1152PubMedGoogle Scholar
  118. Stuart DD, Kao GY, Allen TM (2000) A novel, long-circulating, and functional liposomal formulation of antisense oligodeoxynucleotides targeted against MDR1. Cancer Gene Ther 7(3):466–475PubMedGoogle Scholar
  119. Tian WM et al (2005) Hyaluronic acid hydrogel as Nogo-66 receptor antibody delivery system for the repairing of injured rat brain: in vitro. J Control Release 102(1):13–22PubMedGoogle Scholar
  120. Tuncay M et al (2000) In vitro and in vivo evaluation of diclofenac sodium loaded albumin microspheres. J Microencapsul 17(2):145–155PubMedGoogle Scholar
  121. Walsh S et al (2004) Extended nasal residence time of lysostaphin and an anti-staphylococcal monoclonal antibody by delivery in semisolid or polymeric carriers. Pharm Res 21(10):1770–1775PubMedGoogle Scholar
  122. Wang CH, Sengothi K, Lee T (1999) Controlled release of human immunoglobulin G. 1. Release kinetics studies. J Pharm Sci 88(2):215–220PubMedGoogle Scholar
  123. Wang J, Chua KM, Wang CH (2004) Stabilization and encapsulation of human immunoglobulin G into biodegradable microspheres. J Colloid Interface Sci 271(1):92–101PubMedGoogle Scholar
  124. Wright A, Morrison SL (1994) Effect of altered CH2-associated carbohydrate structure on the functional properties and in vivo fate of chimeric mouse-human immunoglobulin G1. J Exp Med 180(3):1087–1096PubMedGoogle Scholar
  125. Wu AM, Senter PD (2005) Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol 23(9):1137–1146PubMedGoogle Scholar
  126. Yang MX et al (2003) Crystalline monoclonal antibodies for subcutaneous delivery. Proc Natl Acad Sci U S A 100(12):6934–6939PubMedGoogle Scholar
  127. Yasui H, Ito W, Kurosawa Y (1994) Effects of substitutions of amino acids on the thermal stability of the Fv fragments of antibodies. FEBS Lett 353(2):143–146PubMedGoogle Scholar
  128. Zhang W, Czupryn MJ (2003) Analysis of isoaspartate in a recombinant monoclonal antibody and its charge isoforms. J Pharm Biomed Anal 30(5):1479–1490PubMedGoogle Scholar
  129. Zhu L et al (2005) Production of human monoclonal antibody in eggs of chimeric chickens. Nat Biotechnol 23(9):1159–1169PubMedGoogle Scholar
  130. Zimmer AM et al (1989) Stability of radioiodinated monoclonal antibodies: in vitro storage and plasma analysis. Int J Rad Appl Instrum B 16(7):691–696PubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2010

Authors and Affiliations

  1. 1.Genentech, Inc.South San FranciscoUSA
  2. 2.Department of Pharmacy & Pharmacology, Epithelial Cell BiologyUniversity of BathBathUK

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