Appears to be getting the short chain oligosaccharides right. Molecular weight distribution, factor Xz and IIa inhibition, Heptest, aPTT, etc. can be equivalent, but the sequence still wrong. This is a characteristic of some of the foreign LMWH generics. I think I was on the right track in saying the various process parameters are the most likely concern. It turns out to affect both the 1,6 anhydrous ring and the short chain oligosaccharides (because non-optimal process conditions cause a cleavage site on the heparin to change). Why this is hard is probably beyond me in any depth, but I'll take a stab . . .
If it takes brute force tweaking of all the parameters -- such as temperature, pH, depolymerization time -- to get the right set, the possible combinations one might have to go through to arrive at the correct settings gets large fast. So knowing the resulting sequence quickly is a big help. Some methods are faster than others.
The more complex the mixture, the more structural possibilities that could give the molecular weight observed . . .
"The sequencing approach presently uses a brute force method because many of the rules regarding the specificity of enzymes that degrade and modify complex polysaccharides are in the developmental stage. Once these rules or constraints are fully developed, more intelligent algorithms such as a genetic algorithm or Monte Carlo optimization could be used to search a much narrower search space for the correct sequence. The combination of more efficient constraints and algorithms will thus lead to a fully automated sequencing approach."
which is from the Science article by the Momenta/MIT crew.
Getting the FDA scientists to understand that stuff was likely a large part of the delay. Also a FDA reorg that caused some of the review process to shift divisions, but that would presumably have affected all the applicants equally.
It is possible that Momenta/MIT have since developed some of those rules for the enzymes. So they were able to reverse engineer the correct process parameters faster because they knew what they had from each try very quickly. If this is the case, then competitors will eventually get it. But it'll cost 'em money, and more importantly an undetermined amount of time.
I would think that if Momenta is the sole generic for more than six months, competitors would have a hard time cracking the entrenched market. Obviously, they could try and the effort would be detrimental to Momenta because of the terms regarding royalties in multiple generic scenarios. But would it be worth it to the competitor to bother? Cart somewhat before horse here, for as rkrw points out, it's amazing how much traction the branded products retain (aside: what will all the current SNY enoxaparin reps be doing with themselves? how many will be let go?)
I forget the exact numbers, but it feels as though Momenta is priced only slightly above the range we (royal "we" for IHubbers taking the survey!) figured for the multiple generic scenario. Which is probably why many of us bought this news-induced pullback today.
But as I said above, I am no expert, and while the above could be the sticking point for other applicants, it could be something else entirely. Make of it what you will.
Market Data 
Markets 
AI
