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Abciximab: The First Platelet Glycoprotein IIb/IIIa Receptor Antagonist

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Biopharmaceuticals, an Industrial Perspective

Abstract

Platelet aggregation plays a crucial role in the development of the life-threatening thrombosis responsible for such acute coronary syndromes as myocardial infarction and unstable angina pectoris. Although aspirin has traditionally been the mainstay of antiplatelet therapy, it is neither potent nor specific enough to provide adequate protection against thrombosis. The identification of glycoprotein (GP) IIb/IIIa as the key platelet receptor in the final common pathway of platelet aggregation and the development of therapeutic agents that block this receptor have opened up an entirely new dimension in cardiovascular medicine.

Abciximab is the first of an innovative new class of cardiovascular drugs, the GP IIb/IIIa receptor antagonists. As sùch, it is the first agent that specifically blocks the function of a cellular adhesion molecule, thereby interfering with the adhesion of platelets and inhibiting platelet aggregation.

This chapter will review the development of the first murine IgG1 antibody directed against the GP IIb/IIIa receptor and describe how it was genetically engineered to become the less immunogenic but equally effective human/chimeric antibody fragment c7E3 Fab, or abciximab. The extensive studies that elucidated the mechanisms of action and binding characteristics of the new agent, as well as the pharmacology and toxicology studies that confirmed the safety and antithrombotic efficacy of antiplatelet therapy with an antibody fragment will be discussed. Finally, the chapter will explore in depth the fmdings of three large-scale clinical trials that established the role of abciximab in the prevention of thrombotic complications of percutaneous coronary intervention procedures. Ongoing trials investigating the efficacy of abciximab in the setting of acute myocardial infarction will also be discussed.

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  1. Centocor Inc., Malvern, Pennsylvania, USA

    Robert E. Jordan, Marian T. Nakada & Harlan F. Weisman

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  1. Robert E. Jordan
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  2. Marian T. Nakada
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  1. University of Limerick, Limerick, Ireland

    Gary Walsh

  2. Limerick Institute of Technology, Limerick, Ireland

    Brendan Murphy

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Jordan, R.E., Nakada, M.T., Weisman, H.F. (1999). Abciximab: The First Platelet Glycoprotein IIb/IIIa Receptor Antagonist. In: Walsh, G., Murphy, B. (eds) Biopharmaceuticals, an Industrial Perspective. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-0926-2_2

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  • DOI: https://doi.org/10.1007/978-94-017-0926-2_2

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