Intellectual Property Protection

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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
Fighting Infection in Patients with Cystic
Fibrosis Bill Schwan UW-La Crosse
University of WisconsinLa Crosse
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UW-L
MYCO-PHYTE DISCOVERY GROUP a UW-La Crosse
interdisciplinary initiative
Chemistry Microbiology Biology
University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
General procedure collect ? screen ? isolate ?
screen ? elucidate ? synthesize ? derivatize ?
screen ? screen ? screen
Chemistry Microbiology Biology
X inactivestop X inactivestop active
partition bioassay
crude extract
Isolate active cmpd(s) purify solve
structure search literature
protect IP
activego
initial bioassay (other screens?)
inactivestop
more bio (and tox) screens
synthesis analogs protect IP
pre-clinical studies clinical trials
University of WisconsinLa Crosse
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MYCOPHYTE DISCOVERY
UW-L
the multidisciplinary teamthese people and more!
Chemistry Microbiology Biology
University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY
Chemistry Microbiology Biology
progress / collaborative opportunities
NOVEL ANALOGS
PROJECT
ACTIVITY
STRUCTURE
NOVEL?
SYNTHESIS
PRE-CLINICAL
CLINICAL

300 wild mushroom species with wide variety
of activities
ongoing collaborations w/ WI Native Americans
/ herbal remedies
COULD SHARE CRUDE EXTRACT LIBRARY TO SCREEN FOR
ADDL ACTIVITIES
AND HERE!
NEED HELP HERE
University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
Project MD-2/F250
Screened fungal fruiting body library against
bacteria that colonize the lungs of Cystic
Fibrosis patients Goal Find new antibiotic
University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
What is Cystic Fibrosis?
www.nlm.nih.gov
University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
What is Cystic Fibrosis?

• Homozygous recessive genetic disease
• afflicting Caucasian individuals
• Average lifespan of a CF patient is only 32
  years
• Characterized by chronic bronchial infections
  that
• kill more than 90 of CF patients
• Antibiotic resistance in the bacteria a big
  problem

University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
Screening Protocol

• Screened a library of 260 fungal fruiting bodies
• Used disk diffusion assays for screening
• Target organisms were Pseudomonas aeruginosa
• and Acinetobacter baumannii
• Best hit was against fungus labeled F10/F250
• Expanded the assay to include
• Burkholderia cepacia and
• Stenotrophomonas maltophilia

University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
Disk Diffusion Assays Against Glucose
Nonfermenting Gram-negative Rods
University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
Purification of the Active Drug

• First, thin-layer chromatography
• Second, HPLC separation of active peak
• Elucidation of structure of active drug using
• Mass Spectrometry
• NMR Spectroscopy

University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
Structure of Active Natural Product Drug
University of WisconsinLa Crosse
13
UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
2-AQ MICs Against Glucose Nonfermenting
Gram-negative Rods
University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
What To Do Next?

• Synthesize 2-AQ
• Make analogs of 2-AQ
• Proceed with pre-clinical testing of 2-AQ
• More cytotoxicity testing in vitro
• Safety testing in mice/rats
• Efficacy testing in mice/rats

University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
Possible 2-AQ Analogs
University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
Synthetic Route 1
Merck Patent Approach
University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
Synthetic Route 2
Wittig-Style Approach
University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY GROUP
Chemistry Microbiology Biology
Acknowledgements
Mycophyte Discovery Co-Founders Aaron Monte,
Marc Rott, Joe Toce, Tom Volk UW-L
Helpers Craig Dunek, Kathleen Engelbrecht, Mike
Gebhardt, Aaron McCoy, Ron McKelvey, Maria
Drieta, Will Fiers, Nathan Connell Others Davi
d Lewis, Jim Cook, Maliyakal John Monetary
Assistance UW-L, UW-System ARG and ARG-WiTAG
grants
University of WisconsinLa Crosse
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UW-L
MYCOPHYTE DISCOVERY
business opportunities?
Chemistry Microbiology Biology
University of WisconsinLa Crosse