Intellectual Property and Academic- Industrial Collaboration

Transcription

1 Intellectual Property and Academic- Industrial Collaboration J. Denry Sato, D.Phil Visiting Professor of Industry-Academia- Government Collaboration Hiroshima University Funding Problem for Educational Institutions Government funding for education is decreasing Private funding for education is unpredictable Partial Solution Patent and monetize intellectual property 1

2 Criteria for Patentability The invention must be novel It must be non-obvious to one practiced in the art It must be useful Information must be proprietary (non-public) Functions of Patents Patents protect intellectual property for a set period of time Europe: 20 years from the application date United States: 17 years from award date 2

3 How to Monetize Intellectual Property? Start a company to produce and sell invention Pro: Complete ownership Con: High start up costs, production expenses, and liability Collaborate with an industrial partner License out intellectual property for royalties Pro: Low initial costs, and low risk Con: Reduced income Form a partnership Pro: Higher income Con: Some costs and some risks Case Study 1: Cancer Drug Development Drug: Erbitux, a monoclonal antibody to a growth factor receptor Use: To treat advanced colon cancer & head and neck cancers Pathway: Licensed intellectual property rights to a biotech company 3

4 Drug Development The U.S. FDA approves only new drugs each year Drug development takes years at an estimated cost of 500 to 800 million dollars Most drug candidates fail in clinical trials Approximately 1% entering Phase I safety trials survive Less than 50% survive Phase III efficacy trials Gordon Sato, PhD Sato lab, UC San Diego, 1981 John Mendelsohn, MD 4

5 Hypothesis and Strategy Hypothesis (G.H. Sato) Monoclonal antibodies that blocked binding of required growth factors to their receptors would induce cancer cells to die instead of becoming quiescent. Strategy Raise mabs to cells over-expressing receptors, and screen for antibodies that completely blocked ligand binding. Distinctions from other experimental approaches Deliberate selection of neutralizing antibodies Target antigens were not tumor-specific Antibodies would not be armed with isotopes or toxins Rationale for Neutralizing EGFR Monoclonal Antibodies 5

6 EGF Receptor Structure I II III IV Over-expressed by A431 epidermoid carcinoma cells Purified EGF was commercially available EGFR expressed by 50-70% of cancers Tumor Growth Inhibition In Vivo A431 tumors in nude mice A. A431 cells and mabs given concurrently B. A431 cells and mab given sequentially 6

7 Summary of EGF Receptor Antibody Results Four monoclonal antibodies to human EGF receptors (528, 225, 579, 455) Three antibodies blocked EGF binding (528, 225, 579) Three antibodies inhibited A431 growth and EGF-stimulated fibroblast in vitro (528, 225, 579) All four antibodies inhibited A431 tumor growth in nude mice Proof of principle experiments showing that unmodified neutralizing monoclonal antibodies to growth factor receptors were potential cancer therapeutics. 1990: U.S. patent awarded 1993: Intellectual property licensed by Imclone Systems 7

8 Rubin, et al., ASCO 2000 Refractory colon cancer prior to treatment with C225 Partial response to C225 and Irinotecan after 5 months Erbitux (C225) Phase II Clinical Trial for Refractory Colon Cancer L. Saltz, et al./asco Patients Treatment Response Rate C225 + irinotecan 22.5% C225 alone* 10.9% *L. Saltz, et al. (2002) 57 Patiients Bristol-Myers Squibb agreed to buy 20% of IMCL for $2 Billion 8

9 Erbitux (C225) Phase III Clinical Trial for Refractory Colon Cancer D. Cunningham, et al./asco Patients Treatment Response Rate TTP Median Survival C225 + irinotecan 22.9% (p<0.007) 4.1 months 8.6 months C225 alone 10.8% 1.5 months 6.9 months Clinical trial funded by Merck KGaA Applications for approval in Europe and the US was filed in 2003 Erbitux approved for refractory colon cancer in Switzerland (11/03) and in the US (02/04), and for head and neck cancers (2006) Approved in ~80 countries including Japan. 9

10 Approved and Pending Indications for Erbitux Advanced colorectal cancer (approved 2004) Advanced head and neck cancer (approved 2006) First line colorectal cancer (CRYSTAL PhIII, 2008) 59% RR v 43% for FOLFIRI only (p=0.0025; 540 pts) Non-small cell lung cancer (FLEX PhIII, 2008) Significant increase in survival: 11.3 v mo. for cisplatin only (p=0.04; 1,100 pts) Timeline for Drug Development Antibody generation and characterization: Patent application submitted: 1984 Patent application approved: 1990 Intellectual property licensed: 1993 Clinical trials: FDA approval: 2004 Total time: 23 years 10

11 Costs and Income Costs (total) UC San Diego: research and development $450,000 patent application 20,000 patent maintenance fees 36,000 $506,000 Imclone and partners: clinical trials & production $800,000,000 Income (per annum) UC San Diego: ~ $7,000,000 Imclone and partners: ~ $1,000,000,000 In 2008 Eli Lilly bought Imclone Systems for $6.5 billion Case Study 2: Biotech Start Up Company Goal: To raise money to support research a non-profit research institute (W. Alton Jones Cell Science Center) started a for profit biological reagents company (Upstate Biotechnology) Products for research: Cell culture media, media components and supplements, antibodies Approach: License products from academic labs with in-house production and quality control (royalties paid to investigators and Institutions) Target market: Biological research labs 11

12 Requirements Start up funding: $1 million borrowed from Cell Center Facility: Rented space then custom renovated building Employees: From 2 to ~50 employees in 10 years Milestones 1 st year: two products, two employees and $10,000 in sales 5 th year: 10 employees, $1 million sales, profitable 10 th year: 30 employees, $10 million sales 20 th year: 50 employees, $40 million sales In 2005 UBI was sold to Seralogicals, Inc. for $215 million 12

13 Collaborative Benefits to Labs (Sato Lab) UBI royalties: 5% of sales to both lab and institution Non-exclusive licenses for research applications 3 products: 2 antibodies and 1 growth factor Licenses generated ~$20,000/yr in royalties to lab Summary Inventions and products developed in basic research labs are potential sources of income to labs and universities The monetization of this intellectual property requires patent protection Scientists must be aware of the commercial value of their discoveries, and universities must be aggressive in filing patent applications There are many ways to commercialize discoveries (licensing for royalties, partnering, self-development) with different costs and liabilities 13

14 Thank you for your attention! 14