Prism Forum Wilbanks

Slide 1: open pharma innovation and the commons 15 april 2008 PRISM Forum workshop on open innovation North Mymms, U.K.

Slide 2: property theory

Slide 3: the “digital commons”: standard legal tools, accessible to non- lawyers, rendered in machine-readable form, tilted towards sharing the intersection of law and technology

Slide 4: c 100,000,000 objects on the web 500+ peer-reviewed journals uniprot.org nature precedings PLoS

Slide 5: "merck accounts for about 1% of biomedical research in the world...to tap into the remaining 99%, we must actively reach out...the cascade of knowledge flowing from biotechnology and the unraveling of the human genome...is far too complex for any one company to handle alone" - merck annual report, 2000

Slide 6: why is it hard to capture value from all of this knowledge? most of the useful knowledge is inaccessible most of the useful knowledge is poorly formatted traditional business models don’t support it

Slide 7: open innovation: purposive inflows and outflows of knowledge to accelerate internal innovation expand the capacity of the external market to generate internally useful knowledge the business model is at the center of value creation and capture

Slide 8: depends on the requires both new quantity, quality, legal behavior by R&D availability, and entities and the technical usability of emergence of the knowledge intermediaries

Slide 9: pharma deals with that complexity by limiting false positives Nature Reviews Drug Discovery 7, 197-198 (March 2008)

Slide 10: pharma is already practicing open innovation. the question is why it doesn’t more efficiently.

Slide 11: the problem: it’s a combination of formats and access

Slide 12: knowledge flow drives the processes by which we explore new areas of science knowledge formats dictate our ability to exploit new technologies and processes knowledge access allows us to exploit technologies and accelerate the processes of scientific innovation

Slide 13: 1. access control restricts knowledge flow and blocks open innovation

Slide 14: “papers” IGFBP-5 plays a role in the regulation of cellular senescence via a p53-dependent pathway and in aging-associated vascular diseases

Slide 15: “networked knowledge” IGFBP-5 plays a role in the regulation of cellular senescence via a p53-dependent pathway and in aging-associated vascular diseases

Slide 18: using software to index articles: not allowed. http://orpheus-1.ucsd.edu/acq/license/cdlelsevier2004.pdf

Slide 19: PubMedCentral ~ 1,000,000 articles permissions granted: 50,000 (6% of PMC legal for transformative use) (.003 of all PubMed records)

Slide 20: databases as unique entities, instead of nodes in a network

Slide 21: license propagation: whatsoever you do to the least of the databases, you do to the integrated knowledgebase (the most restrictive license wins)

Slide 22: impossible. http://nar.oxfordjournals.org/cgi/content/full/gkm1037/DC1/1

Slide 23: what about tacit knowledge?

Slide 24: Science Commons materials project academic > commercial research MTA one-click contract software (open source) harvest biobank catalogs for integration standard funder policy for grants

Slide 25: Alzheimer’s Disease Multiple Sclerosis Autism Huntington’s distinct “silos” of funded research Disease

Slide 26: Alzheimer’s Disease Multiple Sclerosis Autism Huntington’s Disease bilateral contracts and deals

Slide 27: Alzheimer’s Disease Multiple Sclerosis Autism Huntington’s Disease “one to many” offers / networks

Slide 28: Provider Lab MTA Recipient Lab tracking deposit fulfillment BRC searching / ordering

Slide 29: key change: commercial is defined by status of USE, not status of USER

Slide 32: 1. access control restricts knowledge flow and blocks open innovation look for places to “flip the default switch” - and make sure the public folks do, too...

Slide 33: 2. technical design choices restrict data integration and block open innovation

Slide 34: “read 189,000 papers” is not the ideal answer.

Slide 35: PDSPki Reactome Gene Ontology NeuronDB BAMS Entrez Gene Antibodies Allen Brain BrainPharm Atlas Literature SWAN Homologene PubChem AlzGene Mammalian MESH Phenotype credit: W3C HCLS

Slide 36: better answers through better formats: Mesh: Pyramidal Neurons prefix go: <http://purl.org/obo/owl/GO#> prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> prefix owl: <http://www.w3.org/2002/07/owl#> prefix mesh: <http://purl.org/commons/record/mesh/> prefix sc: <http://purl.org/science/owl/sciencecommons/> prefix ro: <http://www.obofoundry.org/ro/ro.owl#> select ?genename ?processname Pubmed: Journal Articles where { graph <http://purl.org/commons/hcls/pubmesh> { ?paper ?p mesh:D017966 . ?article sc:identified_by_pmid ?paper. ?gene sc:describes_gene_or_gene_product_mentioned_by ?article. } graph <http://purl.org/commons/hcls/goa> Entrez Gene: Genes { ?protein rdfs:subClassOf ?res. ?res owl:onProperty ro:has_function. ?res owl:someValuesFrom ?res2. ?res2 owl:onProperty ro:realized_as. ?res2 owl:someValuesFrom ?process. graph <http://purl.org/commons/hcls/20070416/classrelations> {{?process <http://purl.org/obo/owl/obo#part_of> go:GO_0007166} union GO: Signal Transduction {?process rdfs:subClassOf go:GO_0007166 }} ?protein rdfs:subClassOf ?parent. ?parent owl:equivalentClass ?res3. ?res3 owl:hasValue ?gene. } graph <http://purl.org/commons/hcls/gene> { ?gene rdfs:label ?genename } graph <http://purl.org/commons/hcls/20070416> { ?process rdfs:label ?processname} }

Slide 37: DRD1, 1812 adenylate cyclase activation ADRB2, 154 adenylate cyclase activation ADRB2, 154 arrestin mediated desensitization of G-protein coupled receptor protein signaling pathway DRD1IP, 50632 dopamine receptor signaling pathway DRD1, 1812 dopamine receptor, adenylate cyclase activating pathway DRD2, 1813 dopamine receptor, adenylate cyclase inhibiting pathway GRM7, 2917 G-protein coupled receptor protein signaling pathway GNG3, 2785 G-protein coupled receptor protein signaling pathway GNG12, 55970 G-protein coupled receptor protein signaling pathway DRD2, 1813 G-protein coupled receptor protein signaling pathway ADRB2, 154 G-protein coupled receptor protein signaling pathway CALM3, 808 G-protein coupled receptor protein signaling pathway HTR2A, 3356 G-protein coupled receptor protein signaling pathway DRD1, 1812 G-protein signaling, coupled to cyclic nucleotide second messenger SSTR5, 6755 G-protein signaling, coupled to cyclic nucleotide second messenger MTNR1A, 4543 G-protein signaling, coupled to cyclic nucleotide second messenger CNR2, 1269 G-protein signaling, coupled to cyclic nucleotide second messenger HTR6, 3362 G-protein signaling, coupled to cyclic nucleotide second messenger GRIK2, 2898 glutamate signaling pathway GRIN1, 2902 glutamate signaling pathway GRIN2A, 2903 glutamate signaling pathway GRIN2B, 2904 glutamate signaling pathway ADAM10, 102 integrin-mediated signaling pathway GRM7, 2917 negative regulation of adenylate cyclase activity LRP1, 4035 negative regulation of Wnt receptor signaling pathway ADAM10, 102 Notch receptor processing ASCL1, 429 Notch signaling pathway HTR2A, 3356 serotonin receptor signaling pathway ADRB2, 154 transmembrane receptor protein tyrosine kinase activation (dimerization) PTPRG, 5793 transmembrane receptor protein tyrosine kinase signaling pathway EPHA4, 2043 transmembrane receptor protein tyrosine kinase signaling pathway NRTN, 4902 transmembrane receptor protein tyrosine kinase signaling pathway CTNND1, 1500 Wnt receptor signaling pathway `

Slide 38: when “freedom” isn’t free: DRD1, 1812 adenylate cyclase activation ADRB2, 154 adenylate cyclase activation ADRB2, 154 arrestin mediated desensitization of G-protein coupled receptor protein signaling pathway DRD1IP, 50632 dopamine receptor signaling pathway DRD1, 1812 dopamine receptor, adenylate cyclase activating pathway DRD2, 1813 dopamine receptor, adenylate cyclase inhibiting pathway GRM7, 2917 G-protein coupled receptor protein signaling pathway GNG3, 2785 G-protein coupled receptor protein signaling pathway GNG12, 55970 G-protein coupled receptor protein signaling pathway DRD2, 1813 G-protein coupled receptor protein signaling pathway ADRB2, 154 G-protein coupled receptor protein signaling pathway CALM3, 808 G-protein coupled receptor protein signaling pathway HTR2A, 3356 G-protein coupled receptor protein signaling pathway DRD1, 1812 G-protein signaling, coupled to cyclic nucleotide second messenger SSTR5, 6755 G-protein signaling, coupled to cyclic nucleotide second messenger MTNR1A, 4543 G-protein signaling, coupled to cyclic nucleotide second messenger CNR2, 1269 G-protein signaling, coupled to cyclic nucleotide second messenger HTR6, 3362 G-protein signaling, coupled to cyclic nucleotide second messenger GRIK2, 2898 glutamate signaling pathway GRIN1, 2902 glutamate signaling pathway GRIN2A, 2903 glutamate signaling pathway GRIN2B, 2904 glutamate signaling pathway ADAM10, 102 integrin-mediated signaling pathway GRM7, 2917 negative regulation of adenylate cyclase activity LRP1, 4035 negative regulation of Wnt receptor signaling pathway ADAM10, 102 Notch receptor processing ASCL1, 429 Notch signaling pathway HTR2A, 3356 serotonin receptor signaling pathway ADRB2, 154 transmembrane receptor protein tyrosine kinase activation (dimerization) PTPRG, 5793 transmembrane receptor protein tyrosine kinase signaling pathway EPHA4, 2043 transmembrane receptor protein tyrosine kinase signaling pathway NRTN, 4902 transmembrane receptor protein tyrosine kinase signaling pathway CTNND1, 1500 Wnt receptor signaling pathway ` this query is probably prohibited in the presence of copyleft / non commercial licensing on the underlying databases

Slide 39: http://hcls1.csail.mit.edu:8890/sparql/?query=prefix%20go%3A%20%3Chttp%3A%2F%2Fpurl.org%2Fobo%2Fowl%2FGO%23%3E% 0Aprefix%20rdfs%3A%20%3Chttp%3A%2F%2Fwww.w3.org%2F2000%2F01%2Frdf-schema%23%3E%0Aprefix%20owl%3A%20% 3Chttp%3A%2F%2Fwww.w3.org%2F2002%2F07%2Fowl%23%3E%0Aprefix%20mesh%3A%20%3Chttp%3A%2F%2Fpurl.org% 2Fcommons%2Frecord%2Fmesh%2F%3E%0Aprefix%20sc%3A%20%3Chttp%3A%2F%2Fpurl.org%2Fscience%2Fowl% 2Fsciencecommons%2F%3E%0Aprefix%20ro%3A%20%3Chttp%3A%2F%2Fwww.obofoundry.org%2Fro%2Fro.owl%23%3E%0A% 0Aselect%20%3Fgenename%20%3Fprocessname%0Awhere%0A%7B%20%20graph%20%3Chttp%3A%2F%2Fpurl.org%2Fcommons% 2Fhcls%2Fpubmesh%3E%0A%20%20%20%20%20%7B%20%3Fpaper%20%3Fp%20mesh%3AD017966%20.%0A%20%20%20%20% 20%20%20%3Farticle%20sc%3Aidentified_by_pmid%20%3Fpaper.%0A%20%20%20%20%20%20%20%3Fgene%20sc% 3Adescribes_gene_or_gene_product_mentioned_by%20%3Farticle.%0A%20%20%20%20%20%7D%0A%20%20%20graph%20% 3Chttp%3A%2F%2Fpurl.org%2Fcommons%2Fhcls%2Fgoa%3E%0A%20%20%20%20%20%7B%20%3Fprotein%20rdfs%3AsubClassOf %20%3Fres.%0A%20%20%20%20%20%20%20%3Fres%20owl%3AonProperty%20ro%3Ahas_function.%0A%20%20%20%20%20% 20%20%3Fres%20owl%3AsomeValuesFrom%20%3Fres2.%0A%20%20%20%20%20%20%20%3Fres2%20owl%3AonProperty%20ro% 3Arealized_as.%0A%20%20%20%20%20%20%20%3Fres2%20owl%3AsomeValuesFrom%20%3Fprocess.%0A%20%20%20graph% 20%3Chttp%3A%2F%2Fpurl.org%2Fcommons%2Fhcls%2F20070416%2Fclassrelations%3E%0A%20%20%20%20%20%7B%7B% 3Fprocess%20%3Chttp%3A%2F%2Fpurl.org%2Fobo%2Fowl%2Fobo%23part_of%3E%20go%3AGO_0007166%7D%0A%20%20%20% 20%20%20%20union%0A%20%20%20%20%20%20%7B%3Fprocess%20rdfs%3AsubClassOf%20go%3AGO_0007166%20%7D%7D% 0A%20%20%20%20%20%20%20%3Fprotein%20rdfs%3AsubClassOf%20%3Fparent.%0A%20%20%20%20%20%20%20%3Fparent %20owl%3AequivalentClass%20%3Fres3.%0A%20%20%20%20%20%20%20%3Fres3%20owl%3AhasValue%20%3Fgene.%0A%20% 20%20%20%20%20%7D%0A%20%20%20graph%20%3Chttp%3A%2F%2Fpurl.org%2Fcommons%2Fhcls%2Fgene%3E%0A%20% 20%20%20%20%7B%20%3Fgene%20rdfs%3Alabel%20%3Fgenename%20%7D%0A%20%20%20graph%20%3Chttp%3A%2F% 2Fpurl.org%2Fcommons%2Fhcls%2F20070416%3E%0A%20%20%20%20%20%7B%20%3Fprocess%20rdfs%3Alabel%20% 3Fprocessname%7D%0A%7D&format=&maxrows=50

Slide 41: “view source” effect: shared problem solving on information aggregation prefix go: <http://purl.org/obo/owl/GO#> prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> prefix owl: <http://www.w3.org/2002/07/owl#> prefix mesh: <http://purl.org/commons/record/mesh/> prefix sc: <http://purl.org/science/owl/sciencecommons/> prefix ro: <http://www.obofoundry.org/ro/ro.owl#> select ?genename ?processname where { graph <http://purl.org/commons/hcls/pubmesh> { ?paper ?p mesh:D009369 . ?article sc:identified_by_pmid ?paper. ?gene sc:describes_gene_or_gene_product_mentioned_by ?article. } graph <http://purl.org/commons/hcls/goa> { ?protein rdfs:subClassOf ?res. ?res owl:onProperty ro:has_function. ?res owl:someValuesFrom ?res2. ?res2 owl:onProperty ro:realized_as. ?res2 owl:someValuesFrom ?process. graph <http://purl.org/commons/hcls/20070416/classrelations> {{?process <http://purl.org/obo/owl/obo#part_of> go:GO_0006610} union {?process rdfs:subClassOf go:GO_0006610 }} ?protein rdfs:subClassOf ?parent. ?parent owl:equivalentClass ?res3. ?res3 owl:hasValue ?gene. } graph <http://purl.org/commons/hcls/gene> { ?gene rdfs:label ?genename } graph <http://purl.org/commons/hcls/20070416> { ?process rdfs:label ?processname} } permutation and recombination

Slide 42: information itself is part of the ICT infrastructure thus end-to-end principles need to apply as well...

Slide 43: open innovation, based on based on technology collaborative innovation, strong good design, can defeat complexity design + increased access, can exploit complexity

Slide 44: 2. technical design choices restrict data integration and block open innovation invest in a well-formatted public domain

Slide 45: commons pharma academics

Slide 46: free as in speech free as in beer free as in a puppy

Slide 47: 3. business model designs affect the ability of business to exploit information flows and block open innovation

Slide 48: if knowledge is going to flow, someone will claim rights on discoveries made with that knowledge. business models must capture and share the value with minimal transaction costs - pre-negotiate.

Slide 49: Health Commons

Slide 50: “some rights reserved” “rights to ramble” for research purposes safe harbors for NTD, orphan disease pre-negotiated IP arrangements escrow institutions

Slide 51: 3. business model designs affect the ability of business to exploit information flows and block open innovation figure out how to share profitably.

Slide 52: challenges 1. how to see your internal information against the external information as well as possible? 2. how to figure out what information flows to create? 3. how to give/get credit for discoveries from information outflows? 4. how to get the biggest, most diverse crowd to work on those problems? 5. how to capture the value created?

Slide 53: call to action. identify internal resources for outflow test-drive collaborations and intermediaries create networks between existing collaborations invest in public infrastructure push policy makers to update the metaphors

Slide 54: thank you wilbanks@creativecommons.org http://sciencecommons.org