What bioprocessing challenges are faced in the development and manufacture of a new Protein C therapeutic?

Over the past few days, we've seen Dr. Mike Ultee has shared with us the differences between a biobetter and a biosimilar and the why the current molecule he's working on is a biobetter.  Today, he takes a deeper look into the development and manufacturing of this therapeutic.

Well, we’ve faced a number of them. I’ll start with just the properties of the particular protein itself. It is an enzyme, but beyond that it’s a proteases. What that means is that enzyme that digests protein. When a proteases has had it purified, it has no sub-strength other than molecules of itself. So, you get auto digestion of the molecule. So, you start to get clips and breaks in the peptide chain as the result of the proteases attacking itself. So, that was one of the challenges that we faced.

Half way through the purification process, the pre-enzyme is activated with another enzyme called “PROM-IN” that results in an active protease – a Protein C material – activated Protein C, sometimes called APC. That is what you need to purify carefully under conditions that minimize any auto digestion.

Some other challenges we faced were the post-translational modification, known as gamma-carboxyglutamic acid, sometimes abbreviated GLA. This is a necessary part of the structure of Protein C and some other proteins that allow it to bind to specific receptors on cells and its targets. We need to ensure that there were good substitutions with the gamma-carboxyglutamic acid. Specifically, this enzyme has nine GLA residues on it. So, looking at the structure we were able to confirm that we got good, effective gamma-carboxyglutamic acid modification on this amino acid sequence as originally produced by the protein. It’s just amino acids and then additional modifications are put on, such as this one.

Download Dr. Ultee's full podcast here.

Dr. Ultee will be further examining this topic with with Kent E. Pryor, Ph.D., Chief Operating Officer,ZZ Biotech during the presentation A New Biobetter Therapeutic – Development and Manufacturing: A Collaboration Case Study at Biopharmaceutical Development and Production Week. For more information on this session and the rest of the program, download the agenda.  If you'd like to join us March 24-27, 2014 in San Diego, as a reader of this blog, register to join us and mention code BDP14BLOG and you can save 20% off the standard rate.

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