"Compugen . . . announced today that it is utilizing its proprietary in silico human transcriptome and proteome and additional computational systems to discover splice variants of known drug targets of high industry interest and of other known proteins with potential to become cancer targets for mAb therapy. This program has resulted so far in the discovery of four novel splice variant proteins predicted to be superior oncology targets compared with the previously known proteins. These four splice variants have entered Compugen’s Pipeline Program and are at various stages of validation.
. . . .
Dr. Zurit Levine, Compugen’s VP of R&D, stated, 'We first selected a list of known proteins and drug targets that meet industry therapeutic criteria. Challenging traditional experimental discovery methods, we then utilized our in silico predictive human transcriptome and proteome, and additional proprietary discovery tools, to systematically discover previously unknown splice variants, which, although expressed by the same genes as the known proteins, have a unique epitope within their extracellular region which would allow the development of specific mAbs. Next, we tested their predicted expression, function and certain other properties compared with the known proteins. For example, several of these candidate targets exhibited a potential unique expression pattern, while others exhibited a potential superiority in their functional or structural characteristics. To date, this process has resulted in four candidate targets with predicted superiority compared with the existing proteins.'”
By way of explanation, over a decade ago it was believed that for every protein in the human body, there was a corresponding gene. Accordingly, we haughty humans believed that our more evolutionarily advanced bodies contained a far greater number of genes than, for example, mice or worms. However, it was also known at the time that in extremely rare instances, a gene could give rise to more than one protein by means of "alternative splicing".
Alternative splicing is a process by which exons of messenger RNA (mRNA), produced by the transcription of a gene and which encode the blueprint for proteins, are reconnected in different ways, resulting in multiple mRNA transcripts and ultimately multiple proteins from the same gene. Alternative splicing had been considered the exception and not the rule, but then along came Compugen.
Based upon its computerized analysis of the data available at the time, Compugen told the scientific world that they were wrong. Compugen initially claimed to the bemusement of experts that alternative splicing occurred in some 30% of human genes. Lo and behold, the Human Genome Project determined that fewer genes exist in the human genome than previously believed, and Compugen was proven correct.
Today, it is thought that more than 90% of multiexonic genes are alternatively spliced, and it is also known that abnormally spliced mRNAs are found in a high proportion of cancerous cells.
The significance of Compugen's announcement on Wednesday? As a result of its decade-long research involving biological phenomena on the molecular level and its mapping of the transcriptome and proteome (all mRNAs and proteins present in the human body), Compugen is saying that it can predict in silico (by computer) and discover splice variant proteins of known monoclonal antibody therapeutic (mAb) targets. In addition, Compugen can predict those splice variants having a unique extracellular epitope, a prerequisite for mAb therapy. Thus far, four of these Compugen-discovered splice variant proteins have been predicted by Compugen to be superior to known protein targets.
Superior mAb oncology targets can mean better specificity, with resultant higher efficacy and fewer side effects.
Monoclonal antibody drugs, which primarily target cancer and autoimmune disorders, today amount to more than 30% of the global biologic drug market and could have total sales of some $50 billion by 2013. Without mAb targets, one of Compugen's areas of expertise, there can be no mAb therapeutics. (For an explanation concerning mAbs, see: http://jgcaesarea.blogspot.com/2009/10/monoclonal-antibodies-mabs-for-dummies.html)
What significance might this hold for pharma companies developing mAb therapies? Compugen believes that it can provide the pharma industry with multiple mAb target candidates. Moreover, before spending tens or hundreds of millions of dollars developing a mAb therapy based upon a potential target, pharma companies can consult with Compugen and learn whether there might be splice variants or protein family members that could result in better therapies.
[As noted in prior blog entries, I am a Compugen shareholder, this blog entry is not a recommendation to buy or sell Compugen shares, and in mid-September 2009 I began work as a part-time external consultant to Compugen. The opinions expressed herein are mine and are based on publicly available information. This blog entry has not been authorized or approved by Compugen.]
First rate, extremely helpful, thank you.
ReplyDeleteHi, Jeffrey!
ReplyDeleteIt is all very educational. There are "extracellular epitopes"! They are implicated in cancer!
AJH and Marina, thank you.
ReplyDelete