Replies to post #119191 on Biotech Values

[biotech jim]

Your question #4, here is the link that does not work for me (n=2):

http://www.peptimmune.com/uploads/news/peptimmune_citizen_petition_1012010.pdf

I will have to go back through the messages that I read over the past 3 days to get the information to the first 3 questions. Will do that shortly as it will take some time to locate.

Nice board you have here!

[biotech jim]

OK, DD, I found the original message posted, and it was from a message by investorgold2002 (your Question 1). He or she quoted:

Glatiramer acetate partially cross-reacts with myelin basic protein (MBP) on both the humoral and cellular levels. In addition, it competes with myelin-associated peptides including myelin oligodendrocyte glycoprotein (MOG) and proteolipid protein (PLP) for binding to the MHC
class II molecules.9 Glatiramer acetate binds with high affinity to MHC Class II molecules on the surface of antigen presenting cells.10 In vitro studies demonstrate that the affinity of glatiramer acetate is sufficient to competitively displace MBP, MOG and PLP from MHC II.9
"Specificity of glatiramer acetate binding is demonstrated by the observation that anti-MHC II DR antibodies but not anti-MHC I or anti-MHC II DQ antibodies inhibit interaction of glatiramer acetate with MHC II.9 Induction of suppressor T-cells has been demonstrated experimentally. T-cell hybridomas established from spleen cells of glatiramer acetate treated animals were shown to adoptively transfer resistance to EAE in untreated animals and to inhibit antigen-specific proliferation and interleukin-2 (IL-2) secretion of an MBP-specific T-cell line.11 Inhibition of MBP-specific effector T-cells by glatiramer acetate has been demonstrated in several in vitro studies. In the
presence of antigen presenting cells, glatiramer acetate competitively inhibits proliferation and IL-2 and interferon gamma secretion by human MBP-specific T-cell lines while having no effect on T-cell lines specific for other antigens. Glatiramer acetate alone does not stimulate proliferation,12,13 IL-2 secretion12,13 or cytotoxic responses in human MBP-specific T-cells14. In addition, glatiramer acetate has been shown to inhibit MBP-specific T-cell cytotoxicity..."

Question 2. The above quoted paragraph cites many "activities" of the copolymer, both cellular and humoral related activities. These are not proven biomarkers, since we do not know which one or ones are essential for "anti-MS activity". Animal models for MS are in my opinion only partially relevant, if at all (eg, EAE model in rodents or other species IMO not relevant IMHO).

Question 3 relates to "validated", which in my view would mean necessary and sufficient to be responsible for the disease alleviation. In this context, necessary and sufficient could be both marker(s) of cellular and/or humoral immunity.

Further, I view it essentially impossible to do a PK-PD study when your pharmacodynamic measure does not take into consideration the "necessary and sufficient" point mentioned above.

That does it for my beginner membership limit on posts for at least today, which allows 3 posts until some "higher body" approves my membership/posts.