UPDATE : Monday, June 1, 2020
Techniques for biobetters get ever more advanced
  • By Jeong Sae-im
  • Published 2019.04.29 11:48
  • Updated 2019.04.29 11:48
  • comments 0

Korea’s biotech industry is stepping up efforts to develop biobetters -- upgraded versions of a biologic -- with various techniques aiming to improve the short half-life and low activity of protein drugs.

The Pharmaceutical Society of Korea held a spring academic forum on the “Present and Future of Protein Drug Development,” at the Millennium Seoul Hilton, Friday. Yoon Jae-seung, CEO of PanGen Biotech, introduced the latest technology to develop a biobetter at the forum.

PanGen Biotech CEO Yoon Jae-seung speaks at a forum on protein drugs at the Millennium Hilton Seoul, on Friday.

A protein-drug helps supplement deficient proteins caused by a disease or a genetic disorder. Genentech’s Humulin, the world’s first human insulin produced by recombinant DNA technology in 1982, was the first successful protein drug. In 1986, the protein drug sector made significant progress with the development of a human tissue plasminogen activator (tPA), a thrombolytic agent using mammalian cells.

About 80 percent of newly registered protein drugs over the past five years used mammalian cells. Currently, 70 percent of protein medicines in the market use Chinese hamster ovary (CHO) cell lines. Building cell lines and processing development stages are deemed very significant in developing protein drugs, compared to chemical medicines.

Yoon said that cloned products produced different shapes of isoforms during the expression in CHO cells. “It is difficult to distinguish clones that make the most of isoforms that can be used as drugs,” he said.

So far, protein therapeutics have had shortcomings such as short half-life and low activity. Biobetters can overcome such demerits with various protein modification techniques.

One of the successful biobetter development examples includes a protein structure analysis. Thrombolytic agent Retavase was a biobetter product that enhanced the original Activase, a drug with 527 amino acid and short half-life. After recombining expression with deletion of several domains and reducing amino acid to 357, Retavase had a long half-life.

Yoon also introduced another technique to increase glycosylation to alter proteins. This technique was used for the biobetter Aranesp, which was derived from anemia treatment Epogen. “Epogen containing three N-glycosylations had a short half-life and patients had to take the medication three times a week. By replacing this with five amino acids, Aranesp’s half-life increased three folds,” Yoon said. “There are many biobetters in development using the technique to increase glycosylation.”

Other major research topics will include proteins fused with Fc and Albumin, protein therapeutics for target-based therapy by blending Receptor-Fc, a therapeutic protein with CPP (cell penetrating peptide), and newly emerging nanobodies, Yoon pointed out.

“We have to remember the recall of Omontys, which was released in the U.S. in 2012 but later withdrawn due to serious adverse reactions including heart disease and death,” he said. “Active studies on the mutations of proteins to make a better protein drug do not always result in success.”


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