LATEST DEVELOPMENTS IN BIOTECH PATENTS Carine van den Brink 18 April 2012

Introduction Europe: Biotech Directive (EU Directive 98/44/EG) Industrial applicability (article 5 / recital 24) Interpretation article 9 Directive Interpretation article 6 Directive Case Law European Court of Justice: Monsanto vs. Cefetra July 6, 2010 Brüstle vs. Greenpeace October 18, 2011 US Case Law Supreme Court US Myriad vs. Association for Molecular Pathology (Supreme Court March 26, 2012) Prometheus vs. Mayo (Supreme Court March 20, 2012)

Industrial Application (I) Recital 24 and article 5 of Biotech Directive: industrial application criterion: where a sequence or partial sequence of a gene is used to produce a protein or part of a protein, it must be specified which protein or part of a protein is produced and what function it performs patenting a mere sequence without functionality is not possible since it lacks industrial applicability (it is merely a discovery);

Industrial Application (II) European Patent Office Board of Appeal: T0870/04: Criterion of industrial applicability is not met if: a.Function of protein is complex and not fully understood b.No disease has been identified linked to excess of deficiency of protein c.No other uses have been disclosed T898/05 a.function of protein is at different levels, i.e. molecular (e.g. protease), cellular processes (e.g. apoptosis) and at organism level (e.g. cancer) b.At least one level of function must be described and an immediate concrete benefit derivable from the application T0018/09 a.Concrete benefit may be an assumed therapeutic benefit based on it belonging to a well-known class of receptor and tissue expression data (UK Supreme court Human Genome Science vs. Eli Lilly 2 November 2011: confirmed)

Monsanto vs. Cefetra (I) ECJ July 6, 2010 Case: Monsanto holds EP patent on DNA molecules encoding for herbicide (glyphosate) resistance in soy plants No patent protection in Argentina Monsanto wanted to stop import in EU of soy meal with DNA residue Question: did Cefetra infringe EU patent of Monsanto?

Monsanto vs. Cefetra (II) Article 9 Directive The protection conferred by a patent on a product containing or consisting of genetic information shall extend to all material, save as provided in Article 5(1), in which the product in incorporated and in which the genetic information is contained and performs its function Decision ECJ: Article 9 does not confer patent protection where the patented product (i.e. gene) does not perform the function for which it is patented (irrespective of whether it did perform function previously or will perform function after extraction and reinsertion into living cell) Imported soy meal is “dead”, therefore gene does not perform function Article 9 reflects exhaustive harmonisation within EU member states Date of filing of patent is not relevant

Monsanto vs. Cefetra (III) And now? no absolute product protection for DNA sequences but only “purpose- bound” protection door open for using the method in unpatented countries and then import “dead” resulting material to EU Open questions: Import of (living) seeds (where gene is functional but “silent”) Isolated DNA sequences (diagnostics) or gene therapy vectors where gene is in such state that it will never perform a biological function Answer unclear but ECJ specifically refers to “circumstances such as those of the case in the main proceeding”

Side step to US (I) Myriad vs. Association for Moleculair Patholoy Court of Appeal Federal Circuit (29 July 2011) overruled previous decision by District Court New York March 2010 cDNA is patentable (different from human DNA since introns are spliced out) Isolated human DNA is patentable (2:1) (the cleaving of the isolated DNA from its chromosomal environment creates structure different from natural DNA) Method for comparing and analysing human genes is not patentable (“lacks any transformative step”, Bilsky criterium) Method for screening potential cancer therapeutics is patentable (growing host cells in presence or absence of cancer and then determining growth rates includes transformative steps) Both parties appealed to Supreme Court. Supreme Court reverted back to Court of Appeal on March 26, 2012 in view of Prometheus decision

Side step to US (II) Prometheus vs. Mayo (Supreme Court March 20, 2012) method for optimizing therapeutic efficacy by (a) administering a class of drugs (thipurines) as treatment of autoimmune disease and (b) determining the level of a specified metabolite wherein a level below treshold indicates a need to increase drug and level above treshold indicates a need to increase” Is unpatentable: not specific application but merely claims laws of nature (discovery where metabolite treshold is) Consequences for patents of Myriad still unclear: method claims (may be in danger) DNA product claims (not directly affected by Prometheus decision)

Brüstle vs Greenpeace (I) ECJ October 18, 2011 Article 6 Directive: Inventions are unpatentable where their commercial exploitation would be contrary to ordre public or morality; Unpatentable (e.g.): (a)[process cloning humans]; (b) [process for modifying germ line identity]; (c) uses of human embryos for industrial or commercial purposes; (d) […]

Brüstle vs. Greenpeace (II) Brüstle held patent on isolated and purified precursor cells derived from human embryonic stem cells with the potential to develop into neuronal cells as treatment for Parkinson’s disease. Brüstle used human blastocysts which had to be killed for deriving the embryonic stem cells Questions asked by German court of appeal: What is an embryo? Does scientific research fall under “industrial or commercial purposes? what if the use of embryos is not in patent itself but a requisite for the applicability of the invention?

Brüstle vs Greenpeace (III) Decision ECJ: An embyro includes all cells that are capable of developing into a human being and includes: Fertilized cells from day one as long as they are totipotent; Non fertilized cells where a nuclear of a human cell is implanted and stimulated to develop; Parthenogenesis Pluripotent cells are not an embryo (not capable of developing into a human being) but: if the invention requires prior destruction of a human embryo (even long time prior to invention), it is not patentable. Brüstle method: the blastocyst needed to be destroyed by obtaining the embryonic stem cells so not patentable.

Brüstle vs Greenpeace (IV) ECJ: Use of embryo’s for scientific research purposes is also form of industrial and commercial application (already filing a patent is such form) Interpretation of Biotech Directive is binding on all member states And now?: Induced pluripotent cells derived from adult cells are allowed. But: techniques could advance to induce totipotent cells Using embryonic pluripotent stemcells without killing embryo (but patent application should express that a technique is used that does not kill embryo) Banking on other forms of protection (know how, data exclusivity)

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