1. Owning the Genome Gene Patents: Their History – and Are They History? Jim Evans MD, Ph.D University of North Carolina at Chapel Hill

2. What is Patentable? Patentable subject matter includes: –Machines & Manufactures –Compositions of matter –Processes –Improvements thereon One cannot patent: –Abstract ideas –Laws of nature (including pure mathematical algorithms) –Products of nature

3. Patent Requirements in the US To be granted a patent in the US requirements are: –Novelty –Utility Must be specific, substantial and credible –Nonobviousness Most subjective test Would a person of ordinary skill in the art have thought of it as an obvious advance over entirety of prior art?

4. Patents as Tradeoffs Government grants a right of limited duration (typically 20 years from filing) to prevent others from making, using, selling or importing the claimed entity. In return for this right, the patentee discloses the invention to the public –Thus presumably fostering further research and development

5. Patents on Genes & Life Forms The USPTO and courts have a century of tradition allowing the patenting of chemicals isolated from nature through human innovation –1911: Adrenaline (Parke-Davis v HK Mulford) –1923: Insulin –1958: Prostaglandins –1980: Genetically engineered microorganism (Diamond v. Chakrabarty; US Supreme Court)

6. Patenting Genes Amgen v. Chugai (Fed. Cir. 1991) Patenting of the erythropoetin gene –A protein synthesized by the kidneys which stimulates the production of red blood cells by the bone marrow –Significant therapeutic uses to treat anemia Claim: “A purified and isolated DNA sequence consisting essentially of a DNA sequence encoding human erythropoietin” The gene is what is patented, not the process for making it Why is this gene not a product of nature?

7. Claims in Amgen Patent Isolated –Outside of body Purified –Removal of introns (non coding, non-essential parts of gene) Not found in exactly this form in nature –cDNA is not found in nature Is this a legitimate difference or a “lawyer’s trick”?

8. “Gene Patents” are Highly Heterogeneous Specific claims are critical and differ among gene patents Claims may include: –The genomic version of the gene –A cDNA –Specific mutations –“Methods” Claims, e.g. an association between a sequence alteration and risk of disease 8

9. …Are Highly Contentious Arguments over basic (101) patent eligibility Arguments that directly invoke morality and ethics –Reflecting the importance and personal nature of one’s genome …And Common ~20% of the human genome is under patent

10. Patents and Their Raison D’etre Patents exist for a specific aim –“To promote the progress of science and useful arts, by securing for limited times to authors and inventors the exclusive right to their respective writings and discoveries” - US Constitution, Article I, Section 8 The Patent system was not created to stimulate commerce as a primary goal –It was created to promote a social good, by harnessing commerce in certain ways –In articulating criteria for patenting, the founders recognized that too much or too little patent protection could be problematic

11. Perceived Benefits of Gene Patents Induced investment Stimulation of commercialization Empowers the “little guy” to enhance innovation Gene patents are only one small part of a complex system that has generally worked well Harm has not resulted from >2 decades of gene patents Moral arguments –“Natural Rights” –Imperative to drive innovation

12. Perceived Problems of Gene Patents Inhibition of research Harms to patients due to inhibition of access –Including 2 nd opinions and verification testing Inhibition of competitive markets –Huntington & CF vs. BRCA and SCA –Inhibition of product improvement Creation of patent thickets Moral arguments –Genes are natural substances –The genome is a shared legacy –Genes are uniquely “ours”

13. A “Perfect Storm” Emerging technology has made whole genome sequencing a practical and affordable reality Such technology has great promise for medical application But about 20% of human genes have patent claims upon them Each time we engage in WGS we are almost certainly violating thousands of patent claims –Not necessarily ones hinging on “isolation” but certainly various association patents –Even to find out if we are would require countless (billable!) hours of attorney time –Concerns of hampering application & innovation

14. Proposed Solutions Legislative –Banning gene patents all-together –Providing exemption to infringement for the diagnostic use of gene patents Protecting their use in arenas like therapeutics where the patent incentive may be more justifiable –As SACGHS recommended to Secretary Sibelius & exists in certain European countries Judicial –Myriad, Bilski, Prometheus Reactive May result in confusing and fragmented policy Judges are usually loathe to set policy by rulings Patent pools, royalty arrangements –Little traction thus far Ignoring the problem and hoping it goes away… –It just might Expiration of gene patents Momentum…widespread ignoring of gene patents is the rule in some contexts now Advances in technology Won’t solve the problem of some specific claims, including methods claims 14

15. ACLU vs. Myriad Genetics Law suit filed in May 2009 by ACLU –Plaintiffs include patients, physicians and professional organizations Alleges Myriad’s BRCA1/2 patents unconstitutional –Prevent “2 nd opinion” and verification testing Decision by Federal Judge Robert Sweet invalidated Myriad patents –Reasoning that a gene is, at its essence, a carrier of information –As such, it performs the same role in vivo as when purified and thus a purified gene is not different and therefore not patentable Defense (Myriad) argued primarily along “composition of matter” lines, arguing that an isolated gene is a qualitatively different entity than a gene in the body

16. Winding Through the Courts Court of Appeals for the Federal Circuit ruled (2-1): –Genes are patentable as novel “compositions of matter” (2-1) They were very focused on isolation involving the breaking and formation of covalent bonds –Unanimously ruled against Myriad’s broad “methods” claims i.e. association itself of a mutation with predisposition to cancer is not patentable SCOTUS granted certiorari but immediately remanded back to CAFC –Look at results of Prometheus case (unanamously overturned a broad methods claim related to drug dosing) Now back with SCOTUS to determine whether they will again grant certiorari

17. Things to Think About Is an isolated gene sufficiently different from a native gene to deserve patent protection? Does altering it, (e.g. making a cDNA, breaking bonds, etc.) allow that bar to be met? Are “methods” claims legitimately patentable? –e.g. an association between a variant and disease or risk How will the advent of NGS play out? Licensing may be more important than patenting issues The raison d'être of patents: “to promote the progress of science and useful arts” –Patents are not designed to primarily stimulate commerce; their ultimate rationale is to promote social good 17