Replies to post #46742 on Biotech Values

[dewophile]

CTP approach
I'll chime into this discussion with what I do know about using CTP to modify properties of proteins. I don't know the particulars of the "CTP approach" this company intends to use, but there are examples of products already out there using CTP and CTP-like modifications. The one example I can think of is FSH-CTP, currently in phase 3 development. this was based on the observation that LH and hCG act on the same receptor, are highly homologous through the first 135 or so amino acids, adn differ primarily at the carboxy termini, with hCG having an added 35-40 AAs. biologically the difference between the two seems to be stricly related to half-life, with hCG having about a 24-36 hour t1/2 compared ot LH of 20 min or so. th eCTP of hCG is heavily gycosylated, and presumable the 4 o-linked sugars account for the half-life difference. organon tacked on the CTP to native FSH and voila - it did not impact binding and activity and extended half-life by 2-3 fold over wild type FSH
so in this particular example the key is the glycosylation
it should be noted that in addition to 0-linked sugars, there are examples of adding site-specific n-linked glycosylation signal sequences (aranesp), and I doubt the IP covers N-linked glycosylation
the advantage of N-glycosylation over CTP is that oen can control the number of glycosylation sites more precisely because N-linked signal sequences are clearly definted by teh primary AA sequence

I am not familiar with pegylation, but the nice thing about altering glycosylation patterns..it is a one-step process integrated into the primary AA sequence, cell lines are still able to secrete product with efficiency despite the bulkier glycosylation fragments, and there seems to be minimal steric hindrance to receptor binding, as mutants with large numbers of N- and o- linked moieties were shown to be active. lastly, it can be attached at multiple sites on at least FSH without altering binding activity

[gofishmarko]

>> Were you the lone survey vote for Telaprevir? <<

No , I voted for Provenge. I don't recall all of the list , but I doubt if I would have ranked Telaprevir any higher than 4 or 5. Too much still in doubt there.

For me , Provenge has been the most fascinating biotech story in memory , though that may say more about my memory than anything else.

Provenge might not mean much from a " big picture " perspective , or it might be huge. If it turns out that Provenge is delayed for a few years but approved , and then subsequent fine-tuning and combos with other treatments result in dramatic advances in cancer therapy , this decision , in retrospect , will be earth-shaking , IMO. " FDA Roadblock Costs Lives ; Heads Roll ". If Provenge fails eventually , we'll wonder what all the fuss was about.

Even if Provenge is just one of many eventual therapeutic cancer vaccines , by being the first approved it would have represented a dramatic advance and would have given a big boost to the whole field. Since I believe biologics in general , and immune-based therapies in particular , are the only hopes for significant progress in tx. of advanced cancer , and since advances in this area will spill over into others , like autoimmune and infectious disease , any adverse effects of the FDA decision on funding in these areas could have profound consequences. Basically , I think Thornton had it exactly right. Time will tell , I suppose.

JMHO