SlideShare a Scribd company logo
Accelerating Exploration of Chemical and Biological Space for Academic Drug Discovery [email_address] .  www.limr.org  (see research Services—LCGC)
Lankenau Institute for Medical Research (LIMR).  Wynnewood, PA is an non-profit organization of ~22 independent faculty and other principal investigators who conduct basic and clinical research in cancer, diabetes, and cardiovascular disease.  Founded in 1927. “ In medicine, hope springs from research”
Summary ,[object Object],[object Object],[object Object]
American Academia: A Golden Goose of Innovation? $100 Billion $500 Billion Bayh-Dole Act 1980
Strangling a Golden Goose The COX-2 Story
Greasy Aryl Polar Celebrex Greasy Aryl Alkyl Acidic Ibuprofen
The COX-2 Story: Timeline 1992:  Patent filed 1992:  Merck and Searle begin COX-2 program  1998:  Celebrex approved, 6 months later Vioxx approved 4/11/2000:  U.S. Patent No. 6,048,850 (the '850 patent) issues (‘kitchen sink’) 4/12/2000: UR initiates suit against Searle (Pfizer) 3/5/2003: UR looses up to Supreme Court October, 2003:  NIH Roadmap announced
Why UR Lost “ Because the inventors here simply failed to take the last critical step of actually isolating a compound, or even developing a process through which one of skill would be directly led to such a compound, this patent involves "little more than a research plan," the court concluded. ( http://pub.bna.com/ptcj/006161.pdf ). ‘ The University had claimed a method requiring, yet  provided no written description of, a compound that could  inhibit COX-2 and, therefore, the patent was invalid.’
"We are the National Institutes of Health, not the National Institutes of Biology," Elias A. Zerhouni, M.D. says.  "We need to reengineer how we apply our research to humans."  ( http://www.the-scientist.com/2004/2/16/44/1 ) New Roadmap for  21 st  Century Translational Research
Harbinger of Change
 
Proboscis for Probes? volume 5 number 7 JUly 2009  nature chemical biology
http://genome.gov/Pages/About/OD/ReportsPublications/AustinHHT060806.pdf With New Models In place
‘ High Throughput’ Screening? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Self Deconvoluting Compressed Libraries ,[object Object],[object Object],[object Object]
Important Product Usage and Safety Information The ABBOTT PRISM HIV O Plus test (Human Immunodeficiency Virus Types 1 and 2 (E. coli, B. megaterium, Recombinant) Antigen and Synthetic Peptide)  can be used by laboratory professionals to screen individual donations  of blood for antibodies to HIV-1 (anti-HIV-1) Groups M and O and /or antibodies to HIV-2 (anti-HIV-2). ABBOTT PRISM HIV O Plus can also be used as an aid in the diagnosis of HIV-1/HIV-2 infection.  This assay has not been validated for use with pooled specimens  and is not intended for use on cord blood specimens.
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object], Relevant References Suggest Productive Paths Forward
MX 1-10 epsilon delta gamma beta alpha
New Approaches, Software and Data Mining www. ceuticalsoft .com
The retinoblastoma tumor suppressor pathway contains multiple oncogenes (green) and tumor suppressors (red) and is dysfunctional in almost every human tumor Münger K PNAS 2003;100:2165-2167
[object Object],[object Object],[object Object],Kindly provided by D. Ferra, Wistar Institute)  High Signal Add E2F – specific 1° Ab Wash Add HRP-linked 2° Ab  Wash Add luminescence substrate Wash
Pilot Run Library OCL009 9 E7-inhibitors—pRB/E2F
Trends Observed for Hit Categories E7/pRB-E2F    Conf. Rate
Fructosamine –3-Kinase Pathway in Diabetes Fructoselysine Glucose + Lysine Fructoselysine-3- Phosphate FRUCTOSAMINE- 3- KINASE 3DG  + LYSINE  + Pi Glycated Protein DIET DIABETICS Fructoselysine Glucose  + Lysine Fructoselysine-3- Phosphate 3DG  + LYSINE  + Pi Glycated Protein NON-DIABETICS Diabetic complications Nephropathy Retinopathy Neuropathy Kindly provided by Dynamis Therapeutics Inc.
ADP
Universal Kinase Assay
Pilot Run Library OCL009 9 FN3K Inhibitor Screen
Pilot HTS Results Library LCGC-OCL-009 HTS Results 8 x 8,000 compounds = 64K
Advanced, Innovative  Compound Management Strategies
 
NanoTube Automated Repository System ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Indelible Audit Trail -20  o C Operation Consolidate Molecular Diversity Collections Maxiprep  genomic DNA extractions  for molecular epidemiology studies and biorepositories.  CA Garcia-Sepulveda et al.,  Mol Biol Rep. 2009 Jul 17 Toward  noninvasive genomic screening  of lung cancer patients.  L V Sequist et al., Journal of Clinical Oncology, Vol 27, No 16 (June 1), 2009  epsilon delta gamma beta alpha Abbreviated HTS
FIGURE 3
Present Biorepository Practice
 
Summary ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Acknowledgements ,[object Object],[object Object],[object Object],[object Object],[object Object]

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Mel Reichman on Pool Shark’s Cues for More Efficient Drug Discovery

  • 1. Accelerating Exploration of Chemical and Biological Space for Academic Drug Discovery [email_address] . www.limr.org (see research Services—LCGC)
  • 2. Lankenau Institute for Medical Research (LIMR). Wynnewood, PA is an non-profit organization of ~22 independent faculty and other principal investigators who conduct basic and clinical research in cancer, diabetes, and cardiovascular disease. Founded in 1927. “ In medicine, hope springs from research”
  • 3.
  • 4. American Academia: A Golden Goose of Innovation? $100 Billion $500 Billion Bayh-Dole Act 1980
  • 5. Strangling a Golden Goose The COX-2 Story
  • 6. Greasy Aryl Polar Celebrex Greasy Aryl Alkyl Acidic Ibuprofen
  • 7. The COX-2 Story: Timeline 1992: Patent filed 1992: Merck and Searle begin COX-2 program 1998: Celebrex approved, 6 months later Vioxx approved 4/11/2000: U.S. Patent No. 6,048,850 (the '850 patent) issues (‘kitchen sink’) 4/12/2000: UR initiates suit against Searle (Pfizer) 3/5/2003: UR looses up to Supreme Court October, 2003: NIH Roadmap announced
  • 8. Why UR Lost “ Because the inventors here simply failed to take the last critical step of actually isolating a compound, or even developing a process through which one of skill would be directly led to such a compound, this patent involves "little more than a research plan," the court concluded. ( http://pub.bna.com/ptcj/006161.pdf ). ‘ The University had claimed a method requiring, yet provided no written description of, a compound that could inhibit COX-2 and, therefore, the patent was invalid.’
  • 9. "We are the National Institutes of Health, not the National Institutes of Biology," Elias A. Zerhouni, M.D. says. "We need to reengineer how we apply our research to humans." ( http://www.the-scientist.com/2004/2/16/44/1 ) New Roadmap for 21 st Century Translational Research
  • 11.  
  • 12. Proboscis for Probes? volume 5 number 7 JUly 2009 nature chemical biology
  • 14.
  • 15.
  • 16. Important Product Usage and Safety Information The ABBOTT PRISM HIV O Plus test (Human Immunodeficiency Virus Types 1 and 2 (E. coli, B. megaterium, Recombinant) Antigen and Synthetic Peptide) can be used by laboratory professionals to screen individual donations of blood for antibodies to HIV-1 (anti-HIV-1) Groups M and O and /or antibodies to HIV-2 (anti-HIV-2). ABBOTT PRISM HIV O Plus can also be used as an aid in the diagnosis of HIV-1/HIV-2 infection. This assay has not been validated for use with pooled specimens and is not intended for use on cord blood specimens.
  • 17.
  • 18. MX 1-10 epsilon delta gamma beta alpha
  • 19. New Approaches, Software and Data Mining www. ceuticalsoft .com
  • 20. The retinoblastoma tumor suppressor pathway contains multiple oncogenes (green) and tumor suppressors (red) and is dysfunctional in almost every human tumor Münger K PNAS 2003;100:2165-2167
  • 21.
  • 22. Pilot Run Library OCL009 9 E7-inhibitors—pRB/E2F
  • 23. Trends Observed for Hit Categories E7/pRB-E2F    Conf. Rate
  • 24. Fructosamine –3-Kinase Pathway in Diabetes Fructoselysine Glucose + Lysine Fructoselysine-3- Phosphate FRUCTOSAMINE- 3- KINASE 3DG + LYSINE + Pi Glycated Protein DIET DIABETICS Fructoselysine Glucose + Lysine Fructoselysine-3- Phosphate 3DG + LYSINE + Pi Glycated Protein NON-DIABETICS Diabetic complications Nephropathy Retinopathy Neuropathy Kindly provided by Dynamis Therapeutics Inc.
  • 25. ADP
  • 27. Pilot Run Library OCL009 9 FN3K Inhibitor Screen
  • 28. Pilot HTS Results Library LCGC-OCL-009 HTS Results 8 x 8,000 compounds = 64K
  • 29. Advanced, Innovative Compound Management Strategies
  • 30.  
  • 31.
  • 32. Indelible Audit Trail -20 o C Operation Consolidate Molecular Diversity Collections Maxiprep genomic DNA extractions for molecular epidemiology studies and biorepositories. CA Garcia-Sepulveda et al., Mol Biol Rep. 2009 Jul 17 Toward noninvasive genomic screening of lung cancer patients. L V Sequist et al., Journal of Clinical Oncology, Vol 27, No 16 (June 1), 2009 epsilon delta gamma beta alpha Abbreviated HTS
  • 35.  
  • 36.
  • 37.