Replies to post #267365 on Avid Bioservices Inc (CDMO)

[vanessapu]

What do you think our pipeline is worth ?

[Protector]

vinmantoo, if you make such absurd claim then please name one ENTITY that has a PS receptor to bind to that is NOT on a cell type that is in the blood stream.

Furthermore if you are claiming that you can reach a lymphatic endothelial cell, that is non-vascular, then pls explain how drugs get to it. You intended to drain the lymph nodes in the drug?

The fact that you ask about the life span, after my explanation, kind of show that you are only looking at a SNAPSHOT of the immune system and not look at it as a linear progressing system.

I understand better know why you made that claim on PS. I thought you might not have understood it but now I am sure. This is what you wrote (§which by the way contains other errors but is irrelevant for our discussion on PS vs PS receptor binding):

As far as PS, it is exposed on tumors cell, and on apoptotic cells. The latter providing a sink to draw off and reduced the Bavi that might be therapeutic. Estimates for PS exposure on Jurkat cells are 600,000 per cell, and can reach 25 million. Estimates are that there 1are 10,000 PD1 receptors on T-cells. If the same number of inhibitory ligands and receptors are expressed on tumor cells, you get a sense of what Bavi isn't the target of choice. If there were 10 or 12 different inhibitory receptors or ligands on a tumor cell, that adds up to about 100,000 receptors/ligands. Let's use the lower estimate of 1 million PS molecules exposed per tumor cell. Even if you could put enough Bavi in patients to bind 70% of the PS om each tumors cell, and I doubt you could even come close, there would still be 300,000 free PS per tumors cell. That is 3x the number of inhibitory receptors/ligands expressed per tumor cell. You have way more PS than needed to bind the entire bank of 10-12 different inhibitory receptors/ligands.

The lifespan enters in the ABOVE reasoning because you were talking about PS from apoptosis, dying cells). Since the only cell type that plays in our little scenario that can expose such PS to the bloodstream are vascular endothelial cells, their LIFESPAN is important because that indicates what amount of PS may be expected from opoptosis and hence has a DIRECT impact on your statement. Therefor I illustrated with that table that we are not dealing here with cells in an hourly or daily turn-around time but with months to yeras before they enter apoptosis.

If we take an arbitrary amount of such cells, say 100, then the die all 100 over a period of say 1 year. If it where cell in an hourly cycle then they would all die after a few hours and hence would produce the amount of PS of 100 cells EACH HOUR. I think you see the impact on dosimetry.