Worldwide: RNAi Technology Compatibility In The US And EU – Comparisons And Future Perspectives

This paper discusses the differences in patent eligibility in the US and the EU, and how the resulting inconsistencies have specifically affected RNAi research and patents.

Courts around the world have struggled with defining clear distinctions between patentable and unpatentable biotechnological inventions. Gene-editing technology is unlike anything patent systems have seen before and the field continues to rapidly evolve. The changing technology thus challenges both legislators and the judiciary as they attempt to keep patent rules balanced and current. In the landmark case Association for Molecular Pathology v. Myriad Genetics, the US Supreme Court found that naturally occurring DNA sequences were unpatentable. European courts, however, have not yet followed suit, with the European Directive on the Protection of Biotechnological Inventions noting that isolated DNA sequences are patentable subject matter. In fact, the corresponding European patents at issue in Myriad remained valid in the EU despite various oppositions.

RNAi-based research and technology is still in the early stages of its evolution. Thus the relative ease or difficulty of protecting RNAi IP is likely to have a large effect on the growth of this new class of therapeutics.

INTRODUCTION

Developments in the field of biotechnology have brought many new and divisive challenges to intellectual property legislation. Particularly, courts have struggled with defining clear distinctions between patentable and unpatentable gene-related inventions. Over the past decade the US Supreme Court has issued several decisions resulting in a shift in gene-related patent eligibility. These decisions culminated in the landmark case Ass'n for Molecular Pathology v. Myriad Genetics ("Myriad"), where the Supreme Court found that naturally occurring DNA sequences were unpatentable under USC 35 §101 despite the discovery of their association with certain cancers. ¹ European courts have not yet followed suit, with the European Directive on the Protection of Biotechnological Inventions 98/44/EC noting that isolated DNA sequences are patentable subject matter. ² In fact, Myriad's corresponding European patents, though narrow, remained valid in the EU despite various oppositions.³

This paper discusses the effect that differences in patent eligibility on either side of the Atlantic have had on RNAi research and patents. Given that the first ever RNAibased therapeutic (Onpattro) was only approved by the FDA in 2018, this field is still very much in the early stages of its evolution.⁴ The relative ease or difficulty of protecting RNAi IP is likely to have a huge effect on the growth of this new class of therapeutics.

I. RNAi Technology

Ribonucleic acid interference (RNAi) is a naturally occurring, sequence-specific gene silencing mechanism. Double-stranded RNA molecules (dsRNAs) are processed by an enzyme called Dicer to produce short, singlestranded RNA molecules termed small interferin ribonucleic acids (siRNAs). ⁵ These siRNAs are loaded onto a second enzyme, Argonaute, to form the RNA-induced silencing complex (RISC). RISC uses the siRNA as a guide to find complementary mRNA and cleave it. This results in gene silencing (the gene is "switched off") as the mRNA is degraded, which can be useful in treating diseases that are caused by harmful gene expression.⁶

In the context of therapeutics, scientists design duplexes made up of a desired siRNA guide and a complementary second strand, thus resembling natural dsRNAs. ⁷ Scientists then introduce these duplexes into a cell where the Dicer and Argonaute enzymes process the duplex, as if it were natural dsRNA.⁸ After processing, the designed siRNA guide selectively silences genes which have complementary mRNA to that strand. Thus, the therapeutic payload of RNAi technology is extremely similar to the native cellular process, with the main difference being the source of the double-stranded RNA, which is later processed by Dicer and Argonaute to result in single stranded siRNA.⁹

II. Patentable Subject Matter

A. United States

i. General Patent Eligibility

Section 101 of the Patent Act states that there are four categories of patentable subject matter: processes, machines, articles of manufacture, and compositions of matter.¹⁰ Case law further restricts patentability within these categories by stating that "laws of nature, natural phenomena, and abstract ideas" are also not patentable subject matter.¹¹ These restrictions on patentability were created in order to prevent patenting of standard scientific research methods.¹² Because the purpose of patents is to "promote the progress of science and useful arts,"¹³ patenting a basic research tool may over-reach and in fact stunt and impede the growth of innovation.

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Footnotes

1.  Ass'n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 596 (2013).

2.  Directive 98/44/EC, of the European Parliament and of the Council of 6 July 1988 on the Legal Protection of Biotechnological Inventions 1998 O.J. (L 213), 13, 18.

3.  See Johnathon Liddicoat et al. Continental Drift? Do European Clinical Genetic Testing Laboratories Have a Patent Problem?, 27 EUR. J. HUM. GENETICS 997 (2019); see also Gert Matthijs et al., The European BRCA Patent Oppositions and Appeals: Colouring Inside the Lines, 31 NATURE BIOTECH. 704, 709 (2013).

4. See News Release, U.S. Food & Drug Admin., FDA Approves First-of-Its Kind Targeted RNA-Based Therapy to Treat a Rare Disease (Aug. 10, 2018), https://www.fda.gov/news-events/pressannouncements/fda-approves-first-its-kind-targeted-rna-based-therapy-treat-rare-disease.

5. David Bumcrot et al., RNAi Therapeutics: A Potential New Class of Pharmaceutical Drugs, 2 NATURE CHEM. BIOLOGY 711 (2006), https://doi.org/10.1038/nchembio839.

6.  Nat'l. Ctr. For Biotech. Info., RNA Interference (RNAi), NAT'L LIBR. OF MED., https://www.ncbi.nlm.nih.gov/probe/docs/techrnai/ (last visited Nov. 5, 2022).

7. Anastasia Khvorova et. al., Functional siRNAs and miRNAs Exhibit Strand Bias, 115 CELL 209 (2003), available at https://doi.org/10.1016/s0092-8674(03)00801-8.

8. Queta Boese et al., Mechanistic Insights Aid Computational Short Interfering RNA Design, 392 METHODS ENZYMOLOLOGY, 74-75 (2005), https://doi.org/10.1016/S0076-6879(04)92005-8;  see also Bumcrot et al., supra note 5 at 711.

9. Bo Hu et al., Therapeutic siRNA: State of the Art, 5 SIGNAL TRANSDUCTION TARGETED THERAPY 101, 101 (2020), https://doi.org/10.1038/s41392-020-0207-x.

10.  35 U.S.C. § 101 (1952).

11. See Diamond v. Diehr, 450 U.S. 175, 185 (1981).

12.  See e.g. PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1363 (Fed. Cir. 2007) (invalidating a patent because the researchers had “merely used routine research methods”).

13. U.S. CONST. art. I, § 8, cl. 8.

Originally Published by UCLA Journal of Law & Technology, Vol. 28, No. 1

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