Immunex Message Board - Msg: 12608122

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Biotech / Medical : Immunex

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To: Michael Yang who wrote ()	1/19/2000 12:26:00 AM
From: paradigm7241	of 656

Cambridge Antibody Technology and Enbrel I'm new to this board but I thought a little information on Cambridge Antibody Technology (CAT) might be interesting to you since they will compete with Enbrel for its indications. My background is in immunology and I am currently an immunologist and biotech consultant. I don't post very often but I recently posted several messages on the Vical message board if you are interested. I also post occasionally on the biotechnology board at www.labpuppy.com. I've been doing my own research on the company and I am very impressed with their technology. CAT is involved in the production of fully human antibodies much like Abgenix and Medarex but they use a phage display system for antibody selection rather than a hybridoma selection from human Ig transgenic mice. My major concerns about CAT were that phage display would (a) not be able to provide enough diversity to produce antibodies against any given antigen, and (b) produce Ig with poor affinities compared to mAbs produced in "human Ig" transgenic mice due to the lack of somatic hypermutation using CAT's system. I spoke with Kevin Johnson (head of research at CAT) and I believe that CAT achieves most of their diversity from the size of their Ig locus library which is now in excess of 100 billion loci. The library was obtained by cloning RT-PCR amplified Ig loci from a huge amount of human volunteers into E. coli. From my understanding, both Abgenix's and Medarex's mice contain only the human kappa light chain locus, meaning that variation mediated via lambda light chain rearrangement is not utilized. CAT's phage system is limited by the size of its library of "pre-rearranged" Ig genes but as yet an antigen (autogeneic or allogeneic) for which many specific antibodies could not be selected has not been found. While affinity maturation is clearly an advantage in the murine systems, the affinity of CAT's mAbs for their ligands are all in the area of 10 to the negative 12, very similar to those produced in the murine transgenics. CAT has chosen to launch anti-TNF and anti TGF-beta antibodies into the clinic as their lead products. A sensible choice since companies like Immunex have already provided efficacy for them. Compared to Enbrel CAT's anti-TNF mAb binds to TNF with higher affinity which could (a) keep costs down and (b) have therapeutic benefits which are superior or different than that associated with Enbrel. I was also very concerned with the possibility of rejection of CAT's mAbs due to improper glycosylation of the mAbs produced in a bacterial system. I discussed this with Kevin Johnson as well and it appears that CAT has eliminated this problem by first selecting Fv fragments for target antigens using phage display, then ligating the Fc portion to the Fv and cloning this construct into a mammalian expression system, usually CHO cells. I personally started accumulating CAT around the middle of December. It trades on pink sheets under symbol SMBHF. Check them out for yourself at catplc.co.uk. It's always wise to perform DD before investing.

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