Biotech Values

[DewDiligence]

Cerebral stuff from the SRDX ymb:

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Re: Lucentis gets six-month Priority Review
by: foolishpremise (38/M/Vancouver, BC)
03/09/06 01:33 am
Msg: 15450 of 15453

>"Would a binding protein like Lucentis become saturated by ligand before release if a sustained release implant is used?"<

You raise a very interesting point. Perhaps it would depend on the binding affinity. If the binding is essentially irreversible, and the rate the ligand enters the depot is say...comparable to the rate Lucentis leaves, then I would assume the situation you describe would take place (saturation and end of the window of efficacy prior to the release of all the Lucentis).

If say, the binding was weak enough that the ligand came and went and never occupied more than 50% of the binding sites then perhaps you would always have some activity until all the Lucentis was released.

Do you happen to know if the affinity of such antibodies is usually strong enough to be considered irreversible?

>"Or, perhaps more important, would the binding protein act as a reservoir that upon saturation would lead to continued high titers of the ligand?... "<

Would this happen? Lets say all the Lucentis stayed within the depot and was never released. Initially the ligand would be entering and not leaving. As more ligand was bound, the rate at which some of it would loosen and leave the depot would increase. But the rate at which it left the depot would never exceed the rate that it entered - they would just reach an equilibrium.

Imagine a ping-pong table with walls around it to prevent loss of balls, and a large number of balls (that never lose their bounce) moving back and forth at all angles. On one side of the table a portion of a wall is missing so that balls are removed from the system when they strike there...and new balls are introduced by a device which shoots them onto the table every so often.

The total number of balls on the table is determined by the rate that they leave, and the rate that they are introduced. It will reach a steady state figure. Lets say that once you reach that steady state you change the net into a membrane which bounces back balls heading towards the side with the hole 10 times for every time it passes through (analogous to the depot)...you will end up with 10 times as many balls on the depot side but an equal number of balls traversing the net in each direction per unit time. If someone on the side with the hole were blind to what was happening on the other side of the net they would have no idea there were so many balls there, they would see the same number coming back as going over.

It would seem to me that you would never end up with a higher concentration of the ligand than if the device were never introduced at all.

[Posted as a reply to: Msg 15448 by democritusofabdera]
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