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The AAPS Journal

, 21:39 | Cite as

Pharmacokinetic Properties of Humanized IgG1 and IgG4 Antibodies in Preclinical Species: Translational Evaluation

  • Mohammad TabriziEmail author
  • Divas Neupane
  • Sophia E. Elie
  • Harish Shankaran
  • Veronica Juan
  • Shuli Zhang
  • SuChun Hseih
  • Laurence Fayadat-Dilman
  • Daping Zhang
  • Yaoli Song
  • Vaishnavi Ganti
  • Michael Judo
  • Daniel Spellman
  • Wolfgang Seghezzi
  • Enrique Escandon
Research Article

ABSTRACT

Assessment of the factors that regulate antibody exposure–response relationships in the relevant animal models is critical for the design of successful translational strategies from discovery to the clinic. Depending on the specific clinical indication, preclinical development paradigms may require that the efficacy or dosing-related attributes for the existing antibody be assessed in various species when cross-reactivity of the lead antibody to the intended species is justified. Additionally, with the success of monoclonal antibodies for management of various human conditions, a parallel interest in therapeutic use of these novel modalities in various veterinary species has followed. The protective role of neonatal Fc receptor (FcRn) in regulation of IgG homeostasis and clearance is now well recognized and the “nonspecific clearance” of antibodies through bone marrow-derived phagocytic and vascular endothelial cells (via lysosomal processes) is modulated by interactions with FcRn receptors. In this study, we have attempted to examine the PK properties of human IgG antibodies in dog and monkey. These studies establish a translational framework for evaluation of IgG antibody PK properties across species.

KEY WORDS

Antibody Pharmacokinetics Translation 

Notes

Acknowledgments

The authors acknowledge Dr. Jason Goetzmann; Ms. Jane Fontenot (University of Louisiana at Lafayette) and Mr. Walter Knapp (Merck & Co., Inc., West Point, PA, USA) for their support of and contributions to this work.

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Mohammad Tabrizi
    • 1
    Email author
  • Divas Neupane
    • 1
  • Sophia E. Elie
    • 1
  • Harish Shankaran
    • 1
  • Veronica Juan
  • Shuli Zhang
    • 1
  • SuChun Hseih
    • 1
  • Laurence Fayadat-Dilman
    • 1
  • Daping Zhang
    • 2
  • Yaoli Song
    • 1
  • Vaishnavi Ganti
    • 1
  • Michael Judo
    • 1
  • Daniel Spellman
    • 3
  • Wolfgang Seghezzi
    • 1
  • Enrique Escandon
    • 1
  1. 1.Merck & Co., IncCaliforniaUSA
  2. 2.Merck & Co., IncBostonUSA
  3. 3.Merck & Co., IncWest PointUSA

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