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