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Analytical Chemistry

Why Monoclonal Antibody Drugs Get Sticky

Material could serve as water-based ‘grease’ in artificial joints, reducing wear

by Sarah Everts
May 5, 2014 | APPEARED IN VOLUME 92, ISSUE 18

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Credit: NIST
At concentrations needed to deliver monoclonal antibody drugs by needle, individual proteins (left) often form dimers (right) because of electrostatic attraction, making the drug troublingly viscous.
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Credit: NIST
At concentrations needed to deliver monoclonal antibody drugs by needle, individual proteins (left) often form dimers (right) because of electrostatic attraction, making the drug troublingly viscous.

Monoclonal antibodies (mAbs) have become increasingly lucrative drugs, with recent annual profits in the tens of billions of dollars for treatments for various types of cancer, heart disease, and inflammation. But when mAbs, which have few side effects and excellent target selectivity, are concentrated so they can be injected subcutaneously, the solutions often develop a high viscosity that interferes with drug delivery through a thin needle. Now, a team of researchers led by Isidro E. Zarraga, who works in late-stage pharmaceutical development at Genentech, and Yun Liu, an instrument scientist at the National Institute of Standards & Technology, are reporting that the high viscosity is due to the reversible clustering of mAbs into dimers (Biophys. J. 2014, DOI: 10.1016/j.bpj.2014.02.036). The researchers made use of small-angle neutron and X-ray scattering, neutron spin echo spectroscopy, and computer simulations to study the conformations of the clusters and found that they formed at high concentration primarily because of electrostatic attraction. The discovery may help drug developers modify the sequence of mAbs to prevent clustering.

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