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Effect of Hydrolytic Degradation on the In Vivo Properties of Monoclonal Antibodies

  • Chapter
Biobetters

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 19))

Abstract

Monoclonal antibodies (mAbs) are increasingly used to treat diseases such as cancers, autoimmune disorders and inflammatory diseases. They are, however, highly susceptible to chemical modifications that can affect their potency and predispose patients to adverse immunogenic responses. This chapter presents the common routes of hydrolytic degradation of mAbs, their effects on in vivo performance, and the various strategies used to overcome these effects in developing “biobetter” antibody products.

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Abbreviations

AChR:

Acetylcholine receptors

ADCC:

Antibody-dependent cellular cytotoxicity

CDC:

Complement-dependent cytotoxicity

CDR:

Complementarity-determining region

CH:

Constant heavy chain

CL:

Constant light chain

DKP:

Diketopiperazine

EndoF1-3:

Endo-β-N-acetylgluccosaminidases

ER:

Endoplasmic reticulum

Fab:

Antigen binding fragment

Fc:

Fragment crystallizable

GSH:

Glutathione

Ig:

Immunoglobulin

mAbs:

Monoclonal antibodies

MBL:

Mannan binding lectin

MG:

Myasthenia gravis

MR:

Mannose receptor

PDI:

Protein disulfide isomerase

PML:

Progressive multifocal leucoencephalopathy

scFv:

Single chain fragment variable

SLE:

Systemic lupus erythematosus

SpA:

Staphylococcal protein A

SpG:

Streptococcal protein G

VH:

Variable heavy chain

VL:

Variable light chain

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Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, Purdue University, Robert E. Heine Pharmacy Building, 575 Stadium Mall Drive, West Lafayette, IN, 47907-2091, USA

    Balakrishnan S. Moorthy, Bo Xie, Ehab M. Moussa, Lavanya K. Iyer, Saradha Chandrasekhar, Jainik P. Panchal & Elizabeth M. Topp

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  1. Balakrishnan S. Moorthy
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  2. Bo Xie
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Correspondence to Elizabeth M. Topp .

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  1. Centre for Drug Evaluation and Research, Food and Drug Administration, Division of Biotechnology Review and Research III, Office of Biotechnology Products, Silver Spring, Maryland, USA

    Amy Rosenberg

  2. Genentech, Inc., South San Francisco, California, USA

    Barthélemy Demeule

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Moorthy, B.S. et al. (2015). Effect of Hydrolytic Degradation on the In Vivo Properties of Monoclonal Antibodies. In: Rosenberg, A., Demeule, B. (eds) Biobetters. AAPS Advances in the Pharmaceutical Sciences Series, vol 19. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2543-8_8

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