Human Growth Hormone

1. Human Growth Hormone Whitney Laemmli IGSP Center for Genome Ethics, Law & Policy Summer 2005

2. Early hGH Development • 1956-1958: Discovery of naturally-occurring human growth hormone and demonstration of its clinical efficacy • hGH deficiences associated with: hypopituitarism, Turner’s syndrome, kidney disorders, short stature • 1974: Cho Hao Li patent on synthetic hGH • 1974: Cohen-Boyer patent application filed • 1975: Work on recombinant hGH begins at University of California –San Francisco

3. University of California – San Francisco • Peter Seeburg arrives at UCSF in 1975 • Work in the Boyer, Goodman labs • Collaboration with John Baxter • Expression of rat growth hormone in 1977 • Sequencing of the gene for human growth hormone in 1978

4. Intellectual Property at UCSF • Allocation of credit • New connections between academic science and the commercial realm • Conflicts intensified as a result of new commercial interests? A turning point?

5. Exodus to Genentech • 1976: Genentech formed by Robert Swanson and Herb Boyer • 1977: Genentech makes a proposal to AB Kabi on recombinant human growth hormone project • Mid-1978: exodus of UCSF scientists – Seeburg and Shine join Genentech • Transfer of materials and “The Midnight Raid”

6. Genentech’s Success • Plan is to construct a semi-synthetic gene • May 1979: Genentech successfully expresses hGH • July 1979: Genentech files a patent application and announces news publicly • 1985: FDA approves Protropin® for use in children with hypopituitarianism

7. UCSF v. Genentech (1990–1999) • UCSF seeks $1.2 billion in damages from Genentech for patent infringement • Doctrine of Equivalence • Enablement • Willfulness

8. Issues raised at trial • Commercial pressure on Genentech from AB Kabi • Scientific ethics and the 1979 Nature article • Seeburg’s royalties from the UCSF patent • Patenting and inventorship at Genentech • Transfer of materials between academia and biotech

9. UCSF v. Genentech Decision • Jury voted 8 -1 for patent infringement • Enablement charge found not valid • Genentech settled out of court for $200 million • $50 million toward new research building • $30 million to the UC general fund • $85 million split between the patent collaborators • $35 million to UCSF

10. Current Status of hGH • Marketed in some form by 8 companies • Wide illicit use in sports, anti-aging, beauty, etc. • 2003: FDA approved the use of hGH for otherwise healthy children of abnormally short stature • Current academic research on treatment of HIV, heart disease, aging related conditions

11. Citation Trends

12. Publication Trends “The availability of unlimited supplies of recombinant human GH has led, not surprisingly, to an extensive re-evaluation of clinical indications, both in the traditional endocrine setting and in the non-classical areas” ~Michael Sheppard Source: Monson, John P., ed. Challenges in Growth Hormone Therapy. Malden, MA: Blackwell Science, 1999.

13. Patenting Trends

14. Remaining Questions • Impact of the intellectual property history of hGH on its current status and future uses • Comparison of litigation history and licensing behavior in academia and industry • Analysis of the distribution of profits gleaned from hGH • Comparison of UCSF v. Genentech with other court cases involving growth hormone (ex. consolidated Eli Lilly cases)

15. Questions?