Replies to post #13288 on Biotech Values

[elmono]

Hi Dew,

I haven't found out the 'reply to none' trick, so I will add some info on GTCB and antithrombin this way.

You probably know that plasma derived antithrombin is made commercially available in Europe under the trade name ATnativ by Baxter. What I just learned is that another big, but to me relatively unknown company, by the name of Grifols is marketing plasma derived antithrombin under three different brand names. Their most advanced en newest product (in terms of safety, side effects and shelf-live)is called Abinex (You can check out their website). This made me wonder about the real marketpotential for Atryn in Europe, since Abinex can probably be used off-label for the same indications as Atryn. I believe that Grifols might also want to target the US market with this product. I am curious about your view on this.

Another thing I learned is that the EMEA CHMP Blood Group Working Party will probably evaluate the MA application of GTCB and those guys will not convene as early as half september (you can check out the EMEA website for this), so I find it very hard to believe that the CHMP will make a recommendation before half october, first awaiting the opinion of their most important working group.

The last thing you should check out is the following site:

http://www.fda.gov/cber/summaries.htm

Please take a look at the presentations of Dick Scotland, Chris Healey and Rainer Seitz and let me know if you found these informative. I did. There are also some other interesting presentations. Some DD for the weekend I should say :-)

Regards,

Elmono

[DewDiligence]

For chemistry geeks…

Determination of the site-specific and isoform-specific glycosylation in human plasma-derived antithrombin by IEF and capillary HPLC-ESI-MS/MS

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_....

>>
Proteomics. 2005 Sep 7; [Epub ahead of print]

Plematl A, Demelbauer UM, Josic D, - A.

Institute of Analytical Chemistry, University of Vienna, Vienna, Austria.

The glycan structures of the major and more than ten minor populated isoforms of antithrombin (AT) were determined after separation of the isoforms by IEF using IPG strips. The bands excised from the gel were reduced, derivatized by iodoacetamide and submitted to tryptic digestion. The digest was analyzed by RP-HPLC-ESI-MS equipped with a quadrupole ion-trap mass analyzer. MS/MS experiments allowed establishing the monosaccharide compositions in the glycopeptides.

For the major isoform of alpha-AT four identical biantennary glycans with two terminal sialic acids (SA) each, a total of eight SA, were found in full agreement with the literature. In the IEF-band containing this major isoform (pI 5.18) a further, much less abundant, isoform was detected showing a fucosylation on the glycan attached to Asn(155) but being of otherwise identical structure as described above. The isoforms with pI 5.10 were found to include one triantennary glycan, all antennas carrying terminal SA. The occurrence of triantennary structure is site specific, involving the peptides with Asn(135) and Asn(155), alternately.

At pI 5.24 we found those four isoforms that carry the glycans like the main-isoform of alpha-AT but missing one terminal SA. There was no site specificity found for the mono-sialo structure. The isoform at pI 5.31 is the major isoform of beta-AT containing three identical biantennary structures being fully sialylated.

No isoforms (above 0.5% abundance) with two glycans only or three glycans other than beta-AT were detected. Fucosylation was found in the main isoform with an abundance of about 5%, and as expected with all the other isoforms with a comparable abundance.
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