Page 281 - Binder2

To the immune system, these variations are not neutral.
They are identity flags. And when a glycoprotein shows up
bearing the wrong flag, it may as well be an invader.

That’s where the tolerization process begins—not with the
protein’s core function, but with the sugars on its surface.

The Hidden Saboteurs of Consistency

Even when using the same cell line and the same protocol,
slight shifts in temperature, nutrient availability, or
oxygenation can cause glycosylation patterns to drift. A
batch of infliximab made in Belgium may look subtly
different from the same drug made in Ireland—and the
immune system can tell.

This is why batch-to-batch consistency is so hard to
guarantee with biologics.
And why patients can respond well to one infusion, then
react badly to the next.

And it’s not just about safety. It’s about persistence. The
wrong glycan pattern can accelerate clearance, shorten half-
life, or spark an ADA response that shuts the therapy down
altogether. A sugar chain added in the wrong configuration
doesn’t just cause inefficiency—it marks the drug for
destruction.

Designing Out the Problem

The next generation of biologics cannot afford to ignore
this. If immune compatibility is our goal, then

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