The Evolution of patentable subject matter avoiding threats of extinction

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By Laurence MacPhie and Noel Courage

The sequencing of the final nucleotides in the human genome 10 years ago was a landmark event in biotechnology1, 2. Despite rapid progress in the understanding of human genetic variation, many of the promises of genomics, such as personalized diagnostics and medicine, are still at a very early stage of development. Efficient transfer of advances in genetics ‘from bench to bedside’ has proven technically difficult.

Biotechnology companies are also challenged by the uncertainty of unresolved regulatory and legal issues surrounding commercialization of powerful new tools such as genetic engineering, gene therapy and genome-based biotechnology.

In particular, the types of inventions in biotechnology that can be patented have become increasingly contentious. For an invention to be patentable, it must first fall into a category that is considered patentable subject matter. What constitutes patentable subject matter is therefore an important threshold question.

For example, laws of nature, physical phenomena, and abstract ideas are not patentable categories. In Canada, methods of surgery are excluded from patentable subject matter, but are considered patentable in the United States. In a decision involving the Harvard oncomouse, the Supreme Court of Canada held in 2002 that multicellular life forms were not patentable subject matter3.

This prompted concern in some quarters over the scope of protection available in Canada for certain genetic technologies. However, two years later the Schmeiser Supreme Court decision confirmed that isolated, genetically transformed cells were patentable subject matter4. This case showed that patenting the methods and genetic tools for making a transgenic plant could fully protect the invention, even though the transgenic plant itself was not patentable.

Traditionally, inventions in biotechnology in the United States have had relatively little difficulty in qualifying as patentable subject matter. However, a series of recent, questionable court decisions may potentially affect the scope of patentable subject matter for genes and diagnostic methods. As set out below, the law relating to patentable subject matter is still in a state of flux, so inventors should continue to actively research in this area and pursue aggressive patent strategies in order to be able to adapt to any potential outcomes.

Isolated Genes - The Battle over BRCA
On March 29, 2010 a U.S. District Court in New York found the claims in several of Myriad Genetics’ patents on breast cancer genes BRCA1 and BRCA2 invalid as not being patentable subject matter5. This case is under appeal. The claims covered isolated DNA containing the BRCA1 and BRCA2 gene sequences. The decision stated that the purification of a product of nature, without more, cannot transform it into patentable subject matter and that the purified product must possess “markedly different characteristics”.

In this case, isolating the BRCA1 and BRCA2 DNA from genomic DNA and other cellular components was not considered sufficient to render the molecules “markedly different”.

This decision is inconsistent with prior US federal cases that considered gene claims on other grounds involving validity or infringement. Many patent practitioners feel that the Court of Appeals will side with the long-standing practice of allowing claims to isolated DNA molecules and likely overturn the decision in Myriad. Hopefully, the Court will also provide some clear guidance specifically on the patentability of subject matter related to biotechnology and by so doing provide some assurance for investors and companies working in gene technology.

Diagnostic Methods that
Analyze Genes - BRCA & Bilski
There have been inconsistent results in several recent court cases involving diagnostic methods using genetic analysis of patient samples. These cases will all be reconsidered in view of a recent US Supreme Court case, called Bilski v. Kappos6, that set down general principles for determining what is patentable subject matter. We provide a short summary of the diagnostic method cases and Bilski below.

In the Myriad case, the District Court also invalidated claims for methods of “comparing” or “analyzing” BRCA gene sequences to identify the presence of mutations correlating with a predisposition to breast or ovarian cancer. Other method claims were also invalidated that involved screening for potential cancer therapeutics.

The Court stated that the ‘machine-or-transformation’ test for patentable subject matter required that methods be “tied to a particular machine or apparatus” or “transform a particular article into a different state or thing”. The Court ruled that the claimed comparisons of the DNA sequence failed the ‘machine-or-transformation’ test and were unpatentable “abstract mental processes”.

In a case called Classen v. Biogen7, the US federal Court of Appeals applied the ‘machine-or-transformation’ test to invalidate claims for determining an optimal immunization schedule based on comparing the observed incidence of immune-mediated disorders in different treatment groups. In contrast, the same level of court applied this test in the Prometheus v. Mayo8 case to uphold patentability of claims directed towards a method of optimizing therapeutic efficacy of a drug by administering the drug, determining its level and adjusting the treatment protocol. It is difficult to draw general principles from these cases.

The United States Supreme Court subsequently released its decision in Bilski, which clarified that while the ‘machine-or-transformation’ test is a useful indicator of the patentability of method claims, it is not the sole test for determining whether a method is patentable subject matter. Since the diagnostic method cases all appeared to have applied a single test, they will need to be reconsidered using this broader approach. Moving away from a strict, single test should be a positive development for the patent owners. As well, since the ‘machine-or-transformation’ test remains an option, it may potentially provide a “safe harbour” of patentable subject matter for diagnostic methods that can meet the test, such as in Prometheus. The ultimate outcome for diagnostics is still uncertain because the Supreme Court provided limited guidance on how the test should be applied in a biotechnology setting.

On balance, the Bilski decision was encouraging in that the Court did not preclude claims to diagnostic methods and acknowledged that new tests for subject matter patentability may need to be developed to take into account new types of inventions as technology evolves. The Court seemed to suggest that whether a claim is unpatentable subject matter depends on whether it encompasses a ‘fundamental principle’, such as a “law of nature, abstract idea or physical phenomenon”.

Inventors and biotechnology companies should stick to long-term strategies when deciding to pursue patent protection. This is partly because patent applications filed today will not likely be examined for years at which point the law regarding patentable subject matter may have shifted again. Over time, the strongest patent applications are generally those that focus on good science and that skillfully demonstrate an innovative idea and show a clear practical application.

The last decade has seen some spectacular scientific advances in the development of research tools that will support and encourage genetic research, such as the emergence of high-throughput and low cost sequencing platforms. A strong patent system is also necessary to support and encourage genetic research directed towards gene-based technologies and clinically relevant diagnostic tests. Patents are an important asset that attract investment and drive research and development into risky, new genetic technologies. Fulfilling the promises of genomic medicine will require many more years of patient research and investment. Hopefully the courts will adopt a practical approach and avoid a narrow definition of ‘patentable subject matter’ that could create uncertainty, discourage investment in biotechnology and hamper the transfer of scientific advances to the clinic.

References
1.     Lander et al. Initial sequencing and analysis of the human genome. Nature. 2001 Feb 15;409(6822):860-921.
2.     Venter et al. The sequence of the human genome. Science. 2001 Feb 16;291(5507):1304-51.
3.     Harvard College v. Canada (Commissioner of Patents) 2002 SCC 76.
4.     Monsanto Canada Inc. v. Schmeiser 2004 SCC 34.
5.     Association for Molecular Pathology et al. v. U.S. Patent and Trademark Office et al. (“Myriad”) United States District Court, Southern District of New York. 09 Civ. 4515. March 29th, 2010.
6.     Bilski et al. v. Kappos, 561 U.S. __ (2010), opinion issued June 28, 2010.
7.     Classen Immunotherapies, Inc. v. Biogen Idec. (Fed. Cir. 2008)
8.     Prometheus Laboratories, Inc. v. Mayo Collaborative Services (Fed. Cir. 2009)

Laurence MacPhie, Ph.D. (Human Genetics), J.D. is an associate lawyer with Bereskin & Parr LLP’s Biotechnology and Pharmaceutical Practice group. Laurence can be reached in Toronto at 416-957-1684 or lmacphie@bereskinparr.com.

Noel Courage, B.Sc. (Biochem.), LL.B. is a partner with Bereskin & Parr LLP and a registered Canadian and U.S. Patent Agent. His practice focuses on the patenting and licensing of chemical, biotechnological and pharmaceutical inventions. He can be reached in Toronto at 416.957.1655 or
ncourage@bereskinparr.com