Replies to post #2021 on GTC Biotherapeutics (fka GTCB)

[Biowatch]

>proteins that require eukaryotic expression from bacterial expression for activity. Bacteria can produce huge quantities of material intracellularly. Eukaryotic proteins are generally secreted extracellularly in much smaller quantities, but the cellular machinery is able to glycosylate the proteins (this happens after translation of the RNA into protein, which bacteria cannot do). So glycoproteins must be produced in eukaryotes.<

This is a good characterization. Another distinction is that some proteins are hard to produce in bacteria regardless of whether they need glycosylation. And, as Dew stated, some proteins are hard to make in eukaryotic cells, due to clumping or improper folding, so the goats would be a good choice.

Over the years, I believe that there has been a ten-fold increase in the amount of antibodies that can be produced in a given size (volume) of bioreactor. This could be part of why IMCL moved so slowly at finishing there second manufacturing plant.

By [ex] post-facto glycosylation, I meant the ability to modify the glycosylation on a glycoprotein. There is variabilty in the glycosylation pattern on proteins made by a given method, and there may be more even more variability between different methods of making the same protein even if the same cells are used. That was a concern the FDA had with IMCL making Erbitux in two different ways. (If you remember rick_1426's posts on the subject.)

I think glycosylation could be an issue when the FDA gets around to approving "biosimilar" generic proteins. I don't own any, but I've always thought MNTA was an interesting company. They are working on analyzing and characterizing glycosylation (something which used to be fairly hard to do.) This might be what the FDA will want to see to determine bioequivalence.

MNTA is also working on "engineering" the carbohyadrates in glycosylated proteins.

http://www.momentapharma.com/science_technology.htm
http://www.momentapharma.com/overview.htm

Earlier, when I said that GTCB fell on its face before, I was referring to when the FDA asked them for more clinical trial data and then GENZ abandoned them. I don't remember the name of the person I saw speak, and I'm pretty sure he's not there anymore.

I'm not trying to bash, just trying to add some perspective.

[rustyboy]

My rough guess is the potential cost advantage of transgenics remains quite significant--lets says $40 to $60 million
for a goat based platform versus--say $300 to $500 million for a cell culture facility. (Some of you may have some better numbers on this--I'd appreciate any better info.)

Regarding 'industry-wide' capacity, with some 200 Mabs alone in development, I expect 'capacity' will continue to be a real planning issue for many companies. Which leads me to my main point and that is the 'scaleabilty' of production using the transgenic approach is also a key advantage. A company normally has to guess how much capacity they will need when they build a cell culture facility and the capital outlay occurs up front. With goats (or cows or rabbits) a company could not only spend less up front, they then can scale up the herd as demand grows.

Some examples of the difficulties of matching capacity with demand include Biogen/Elan with their Tysabri factory--which they were able to sell to Genentech. Abgenix built a facilty and then the product they built it for failed. Going the other way, several years ago Immunex got Enbrel approved and it was such a hit, they quickly maxed out their factory and their limited capacity angered the public and allowed Remicade to get more RA patients than they otherwise would have.