Business


References 1 Macarron, R, Banks, MN, Bojanic, D, Burns, DJ, Cirovic, DA, Garyantes, T, Green, DV, Hertzberg, RP, Janzen, WP, Paslay, JW, Schopfer, U, Sittampalam, GS. Impact of high-throughput screening in biomedical research. Nat Rev Drug Discov. 2011 Mar;10(3):188-95. 2 McDonald, PR, Roy, A, Taylor, BJ, Price, AR, Sittampalam, S, Weir, S, Chaguturu, R. High throughput screening in academia. Drug Discovery World 2008; Fall: 59-74. 3 Roy, A, Taylor, BJ, McDonald, PR, Price, AR. Hit-to-probe-to- lead optimization strategies: a biological perspective to conquer the valley of death. In Seethala R & Zhang L (Editors), Handbook of Drug Screening, Second Edition, 2009: Informa Healthcare: 21-55. 4Website: http://nihroadmap. nih.gov/grants/fundedresearch. asp. Accessed December 2011. 5 McDonald, PR, Roy, A, Chaguturu, R. The University of Kansas High-Throughput Screening Laboratory part II, enabling collaborative drug- discovery partnerships through cutting-edge screening technology. Future Med Chem 3(9): 1101-1110, 2011. 6Website: http://www.rgs.ku. edu/org/rgs_centers.pdf. Accessed December 2011. 7Website: http://www.slas.org/ screeningFacilities/facilityList.cf m. Accessed December 2011. 8Tai, D, Chaguturu, R, Fang, J. K-Screen: A free application for high throughput screening data analysis, visualization, and laboratory information management. Comb. Chem. High Throughput Screen. 2011 Nov 1;14(9):757-65.). 9 McDonald, PR, Roy, A, Chaguturu, R. The University of Kansas High-Throughput Screening Laboratory part I, meeting drug-discovery needs in the heartland of America. Future Med Chem 3(7): 789- 795, 2011. 10Website: http://www.slas.org/screening Facilities/facilityList.cfm. Accessed December 2011.


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was able to make an affordable solution to meet the database management needs of KU HTSL, without the steep price of a commercial LIMS. KU HTSL freely offers the KScreen algorithms to other AHTSCFs at no cost, and advises in setting up their own database management system.


Medicinal chemistry plus HTS. High throughput screening cores need to stay competitive for federal grants to maintain their funding levels. The Molecular Libraries Probe Production Centers Network (MLPCN) demonstrated the strength of comprehensive screening centres and the aid of medicinal chemists to provide the expertise and technology needed to improve the specificity and strength of screening hits. Academic screening cores need the assistance of medicinal chemists, but very few universities have both a high throughput screen- ing lab and a medicinal chemistry department, such as the one at the University of Kansas and the University of Pittsburgh9. Medicinal chemistry departments are very rare, and are even rarer at medical schools, where drug discovery efforts are needed the most, due to the cutting edge targets being pursued.


Institutional seed funding. The AHTSC facilities play a critical role in enhancing academia’s mission in drug discovery. We have witnessed many drug discovery-related grant applications that did not originally get funded succeed in subsequent submis- sions when a HTS component is included with strong pilot data. Many academic investigators with potentially fundable drug discovery project ideas have been unable to develop strong grant applications due to a lack of pilot data, a critical component to show the granting agencies that the target has been validated, a robust HTS-amenable assay exists, and pilot screening data is encourag- ing. We challenge the upper management in acade- mia to provide seed funding in the range of $25,000 to $50,000 to investigators to develop competitive grant applications. If successful, this modest invest- ment could result in a 10- to 30-fold return on investment, bringing $250,000 to $1.5 million, depending on the type of grant, to support the investigator’s drug discovery research. Not to for- get, a sizeable percentage of the funds received go to the institution towards supporting its Facilities and Administration costs. It’s a win-win scenario for both the investigator as well as the institution!


Intellectual property, technology transfer and roy- alties. The AHTSCFs are keenly aware of the intel- lectual property that might be associated with all


aspects pertaining to the therapeutic target, includ- ing assay novelty, med chem-optimised screen hits, therapeutic relevance of the probes/leads devel- oped. At KU-HTSL we work very closely with the Technology Transfer and Commercialization office in filing provisional patent applications, and navi- gating communications with the interested phar- maceutical industry or disease foundation part- ners. Occasionally, entrepreneurial investigators embark on setting up incubator companies either on campus or in close proximity to the campus and maintain close collaborations with the institution. It is well recognised in recent years that the AHTSCFs are not just ‘fee-for-service’ providers, but are indeed true partners with substantial intel- lectual input in transforming the investigators’ projects into bona fide drug discovery projects. As such, the HTS staff members are often named as co-inventors in patent applications, and the AHTSCFs are the beneficiaries of any royalties that come out of the marketable discoveries. While this scenario is not just quite the case with most AHTSCFs, it is indeed becoming the norm and plays heavily into the self-sustainability of the AHTSCFs. To those AHTSCFs that strictly main- tain a ‘service’ mindset, we caution to look beyond the service fees and publications and glean into patent filings and the potential for royalties for their contributions.


Concluding remarks Rather than work independently, in isolation and against each other, academic screening labs need to recognise the importance and advantages of helping each other, buffering weaknesses and uniting. This is not just for the embitterment of the landscape of drug discovery and patients, but also for our very survival as we each fight for self- subsistence as federal research dollars are waning or shifting to more translational directions. By forming a consortium of allies, academic screen- ing labs will be better able to meet the needs of academic investigators who carry cutting edge research, and apply the ready availability of tech- nology and expertise, as the MLPCN stage of the NIH Roadmap Initiative comes to a conclusion. The proposed steps would eliminate waste, cut costs and improve efficiency, all-important driv- ers of self-sufficiency. The participating AHTSCFs would maintain their autonomy, in the proposed consortia, as long as there is a memo- randum of understanding that has clearly addressed not just publications and revenue shar- ing, but also the stake in intellectual property, technology transfer and any royalties that will be


Drug Discovery World Winter 2011/12


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