Pullan Consulting
Biotech Business Development Consulting
www.pullanconsulting.com and www.lindapullan.com
email: lpullan@msn.com 805-558-0361
Issue #24
Pullan's Pieces
Commentary on Science & Business of Drug Development
For Business Development & Others
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The number of genes does not reflect the complexity of the “Interactome”
The “interactome”, that network of protein : protein interactions (whether binding, inhibiting or stimulating), is about 10x larger for humans than for the fruit fly, despite only about a 2-fold difference in the number of genes, according to the statistical estimates (MP Stumpf et al, PNAS. 2008 May 13; 105(19): 6959-64). Evolutionary changes to the proteins encoded by the genes could enable additional interactions with other proteins, without increasing the number of genes. Making more than 1 protein from a gene also increases the number of possible interactions. These new insights on complexity do not yet include the complexity added by interactions of other kinds of molecules such as small RNAs. As the commentary in PNAS put it, this “interactome” is a measure of our ignorance in understanding the marvels of biology. It is also a cautionary tale against reliance on simple pathway maps and simple species as models in thinking about the effects of a drug or disease.
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First to market or fast follower? Factors driving market success
Drug discovery teams must always wrestle with when to pursue a drug target. When is there enough data to say the target is validated? When is there too much competition? What will be a successful market differentiation years in the future?
A study of 171 drugs approved from 1984-2004 (in 14 therapeutic classes across 32 mechanisms of action) looked at the market success of first-to-market “innovators” versus the “imitators”, drugs with the same target approved after the leader.
About a fourth of the imitators beat the innovator in sales. What were the measurable factors that influenced the ability of the imitator to take the lead position in sales away from the innovator?
· Larger firms were more likely to beat the innovator.
· The greater the remaining patent life of the innovator’s drug, the lower the likelihood the imitator will beat the innovator.
· Longer lag times improved the chance of beating the innovator. Greater imitation time lag between the innovator and the imitator is correlated with greater information about the innovator’s drug that can be exploited to improve differentiation. All other variables held at their means, one additional year increase in the imitation time lag beyond the mean increases the probability of beating the innovator by about 1.4%.
· As might be expected, when new entrants offer improved quality and that quality is visible before purchase, imitators enjoy significant market share.
· Improvements in efficacy (measured here as the number of indications) were more important than improvements in safety (measured as the number of side effects). All other variables held at their mean, one percentage point increase in the number of indications offered by the imitator increases the probability of beating the innovator by 7.1%. The impact of improvement in number of indications is robust across the full range of observed data. All other variables held at their means, one percentage point increase in the number of unique side effects in the imitator decreases the probability of beating the innovator by 0.6%.
Ethiraj and Zhu, Performance effects of imitative entry, Strategic Management Journal, Dec 2007, http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1066901
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Biggest news from ASCO? Erbitux biomarker impact on response.
Perhaps the biggest buzz from ASCO was garnered by ImClone’s EGFR antibody Erbitux.
Erbitux will become a new argument for biomarkers and personalized medicine, since the 55-65% of colon cancer patients who do not have a mutation in the downstream signal KRas benefited from first-line Erbitux, with a 32% reduction in the risk of tumor progression. In patients with a KRas mutation, Erbitux did not provide any benefit. Without analysis of the KRas mutation, Erbitux reduced the risk of tumor progression by only 15%. The KRas mutation biomarker thus defines a patient population with a better response and prevents the Erbitux side effects in the patients who have little chance to benefit.
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When is a little cancer too little to worry about?
The New York Times (Laura Biel, p D1, June 3, 2008) reported on the challenges of increasingly sensitive biopsies of the sentinel lymph node, the lymph node most closely connected to the tumor. Micrometastases, too small to be defined as true metastases, have been increasingly identified over the years, but their prognostic impact remains unclear. At the San Antonio Breast Cancer Symposium in December, researchers reported that women with just micrometastases in their lymph nodes survived as long on average as those with clear nodes, but these women and their oncologists knew of the micromets and that probably influenced the course of treatment. Two national double-blind studies will not provide answers for years. In the meantime, patients must decide whether to risk the swelling and pain from lymph node removal or to live with the worry of a little cancer.
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Update: MedImmune and Genentech settle on Cabilly patent litigation
The fundamental patents on antibody production, Cabilly I and II, continue to make the news. Cabilly II was revoked but is under appeal (as discussed in Pullan’s Pieces #9, http://www.pullanconsulting.com/pieces/newsletters/Newsletter++9 ). MedImmune won the right to challenge the Cabilly patents while maintaining a license (as discussed in Pullan’s Pieces #5 http://www.pullanconsulting.com/pieces/newsletters/Newsletter++5, and Pullan’s Pieces #8 http://www.pullanconsulting.com/pieces/newsletters/Newsletter++8 ).
Now MedImmune and Genentech have settled out of court on MedImmune’s challenge to the Cabilly patent. MedImmune will get the right to licenses under Cabilly for additional products. Genentech said it was not updating its revenue projections from the license. http://www.streetinsider.com/Corporate+News/Genentech+(DNA)+Announces+Patent+Litigation+Settlement+with+MedImmune/3736240.html
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Listen at BIO for discussion of the Quanta Computer vs. LG Electronics Supreme Court Case
The Supreme Court just decided a case that will impact licensing contracts. In Quanta Computer vs. LG Electronics, the Supreme Court ruled that once a product substantially embodying the essential features of the patent claims was sold, it could be resold without LG Electronics getting royalties. The patent for downstream uses was exhausted by the first sale. BIO had written a Friend of Court briefing, discussing the implications for selling genetically engineered seeds and cells which self-perpetuate, and are often sold with restrictions on the use of the offspring unless additional royalties are paid. In addition, BIO asked the Court to think about the implications for research-use licenses and the potential later license for commercial use. If the first sale exhausts the patent rights, research-use licenses (generally cheaper than commercial licenses) may be impacted. In a footnote, the Supreme Court said “LGE's complaint does not include a breach-of-contract claim, and we express no opinion on whether contract damages might be available even though exhaustion operates to eliminate patent damages.” Thus contractual restrictions on post-sale uses may still be a remedy when the user is under a contract, but patent cases are not a remedy.
http://www.patentdocs.net/patent_docs/2008/06/quanta-computer.html
http://www.law.cornell.edu/supct/cert/06-937.html
Two sessions at BIO2008 on Wednesday may touch on this case and other recent decisions narrowing patent rights.
Biopharma IP Strategies in the Post-KSR World Track: Intellectual Property/Legal, Breakout Sessions Wednesday Jun 18, 2008 Time: 10:15 AM - 11:45 AM
Impact of Changing Policy on Technology Commercialization Track: Technology Transfer/Licensing, Breakout Sessions Wednesday Jun 18, 2008 Time: 4:00 PM - 5:30 PM
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Hope to see many of you at BIO!
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Pullan Consulting
Linda M. Pullan, Ph.D.
Biotech Business Development
www.pullanconsulting.com and www.lindapullan.com
e-mail: lpullan@msn.com
805-558-0361
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