October 31, 2015

PTO Issues AIA-Mandated Report on Genetic Testing and Gene Patents

In the debates over the legitimacy of gene patents, one of the central concerns over the impact of gene patenting was whether patients could access second-opinion (confirmatory) genetic testing of positive test results. This circumstance was most acutely illustrated in the BRCA1 and BRCA2 breast cancer gene testing field, where the patents on these genes were held by Myriad Genetics, Inc.. Unlike some other gene patent holders, Myriad did not license other genetic testing laboratories to offer commcercial clinical testing, with the result that almost all BRCA1/2 genetic tests in the U.S. were performed by Myriad. Of relevance here, this meant that patients lacked opportunities for independent assessment of test results that indicated the presence of a mutation in either gene which significantly increased risk of developing breast and/or ovarian cancer. As is well-known now, the Myriad patents were invalidated in the landmark case of Association for Molecular Pathology v. Myriad Genetics in 2013. However, several years earlier, as part of the America Invents Act of 2011 (AIA), Congress instructed the U.S. Patent and Trademark Office (PTO) to conduct a study on the impact of gene patents on the availability of confirmatory genetic diagnosis. The AIA required the PTO to assess the following:
(1) The impact that the current lack of independent second opinion testing has had on the ability to provide the highest level of medical care to patients and recipients of genetic diagnostic testing, and on inhibiting innovation to existing testing and diagnoses.
(2) The effect that providing independent second opinion genetic diagnostic testing would have on the existing patent and license holders of an exclusive genetic test. 
(3) The impact that current exclusive licensing and patents on genetic testing activity has on the practice of medicine, including but not limited to: the interpretation of testing results and performance of testing procedures. 
(4) The role that cost and insurance coverage have on access to and provision of genetic diagnostic tests.
Although behind schedule, the PTO report has now issued. No doubt, assessing the climate of genetic testing against a backdrop of gene patenting has been significantly altered by AMP v. Myriad; it could be argued that the PTO’s report is somewhat obsolete now. However, the agency acknowledges the changes in the field since 2011, and simply advances some modest conclusions and recommendations about the availability of genetic testing in general. From the report:
Although the evidence on each of these points was limited in its scope and mixed in its implications, recent Supreme Court decisions make it unlikely that exclusive provision of a diagnostic test, whether for an original diagnosis or to confirm the original result, will be possible based on patenting and licensing behavior. Patients seeking independent confirmation of diagnostic results will almost certainly be able to find it as long as the demand level for the test (or research interest in the particular gene or condition) supports a market for multiple test providers. For this reason, much of the USPTO’s factual findings may now be superseded by intervening judicial decisions. In view of the altered legal landscape, the USPTO’s recommendations to Congress are limited in scope. 
The first recommendation is to proceed cautiously, monitoring changes in the actual availability of gene-based diagnostic tests from multiple providers. The second recommendation is to consider creating mechanisms to facilitate sharing data on diagnostic correlations in order to build robust databases of the relationships between genetic mutations and the presence, absence, or likelihood of acquiring the relevant medical condition. Data sharing of this kind would promote the most rapid advances in the diagnostic accuracy  of individual tests. The third recommendation is to consider the role of cost and insurance. However, because the USPTO does not have the institutional expertise to make specific recommendations regarding insurance coverage for gene-related diagnostic tests, this report can only emphasize that insurance coverage does appear to play significant a role in access to testing and should be taken into consideration when issues of access are examined. 
It was always a jurisdictional stretch to require the PTO to undertake this kind of analysis; the fact that such a mandate emerged from the AIA illustrates the high level of controversy over the validity of gene patents, an issue that was unresolved at the time of the law’s enactment. The PTO in general is not charged with considering the impact of patenting on market access or health care. However, its observations on the need for data-sharing of genetic correlations to clinical findings is on target. With respect to the BRCA1 and BRCA2 genetic mutations correlated with increased cancer risk, one of the consequences of the Myriad dominance of the testing market through its patents was that the company maintained the repository of most test results for these genes (important gene mutations), and was under no obligation to share them. Loss of its gene patents did not alter the fact that it had established significant genetic databases of clinically relevant mutations in the breast cancer genes. However, resistance to the establishment of proprietary genetic databases of critical genetic mutations has emerged through such initiatives such as Free the Data, and later, with the international genetic data-sharing efforts underway through the Global Alliance for Genomics and Health. Notably, the federally-funded ClinVar was established in 2013, which is an open-access public database of clinically relevant genetic data. However, the PTO report is correct in identifying this phenomenon as a determinant of whether patients are able to receive state of the art interpretations of mutational significance as the basis for medical decision-making. Furthermore, issues of cost and insurance access remain as determinants for consumers, and the patent structure of a genetic testing market will affect cost, but - apart from the notice in this PTO report - ongoing evaluations of patent validity in biotechnology do not consider such issues directly; they are collateral to decisions that are made with reference to the strictures of patent law. However, this report does sketch out an accurate field-wide portrayal of the access determinants that are indirectly influenced by patent rights.

October 28, 2015

High Court of Australia Rejects Myriad Genetics BRCA1 Gene Patents

In 2013, the U.S. Supreme Court invalidated patent claims to isolated BRCA1 and BRCA2 breast cancer genes in the case of Association for Molecular Pathology v. Myriad Genetics, on the basis that genes are not patentable subject matter (see here). Now, the High Court of Australia (HCA) has issued a decision in a case that challenged the legitimacy of patent claims to isolated genes. This month, in the case of D’Arcy v. Myriad Genetics, Inc., the HCA invalidated similar Myriad patent claims on the isolated BRCA1 gene. In contrast to the U.S. patent, the Australian claims were confined to mutated or polymorphic BRCA1 genes that are indicative of cancer risk, but which are central to a patenting strategy that would control much of current BRCA1 genetic testing. The Court’s summary
Today the High Court unanimously allowed an appeal from a decision of the Full Court of the Federal Court of Australia. The High Court  held that an isolated nucleic acid, coding for a BRCA1 protein, with specific variations from the norm that are indicative of susceptibility to breast cancer and ovarian cancer, was not a "patentable invention" within the meaning of s 18(1)(a) of the Patents Act 1990 (Cth) ("the Act").
The term "nucleic acid" includes  two kinds of molecules, deoxyribonucleic acid (DNA) and ribonucleic acid  (RNA), which are found inside a human cell. A gene is a functional unit of DNA which encodes a particular protein produced by the cell. The protein produced depends on the sequence of nucleotides. The BRCA1 gene codes for the production of a  protein called BRCA1.
The first respondent filed a patent which contained  30 claims. Relevantly, Claims 1 to 3 concerned a nucleic acid coding for a BRCA1 protein, and with one or more specified variations from the norm in its nucleotide sequence, isolated from its cellular environment. Those specified variations, characterised as mutations or polymorphisms, are indicative of susceptibility to breast cancer and ovarian cancer. 
Section 18(1)(a) of the Act requires that, for an invention to be patentable, it must be "a manner of manufacture" within the meaning  of s 6 of the Statute of Monopolies. The appellant commenced proceedings in the Federal Court of Australia challenging the validity of Claims 1 to 3 on the basis that the invention claimed did not meet the requirement of s 18(1)(a). 
The primary judge dismissed the appellant's challenge, holding that the invention fell within the concept of a "manner of manufacture”. The Full Court dismissed an appeal from that decision. The Full Court held that an isolated nucleic acid was chemically, structurally and functionally different from a nucleic acid inside a human cell. The invention was a manner of manufacture because an isolated nucleic acid with the characteristics specified in Claims 1 to 3 resulted in an artificially created state of affairs for economic benefit. 
By grant of special leave, the appellant appealed to the High Court. The Court unanimously allowed the appeal, holding that the invention claimed did not  fall within the concept of a manner of  manufacture. The Court held that, having regard to the relevant factors, an isolated nucleic acid, coding for the BRCA1 protein, with specified variations, is not a manner of manufacture. While the invention claimed might be, in a formal sense, a product of human action, it was the existence of the information stored in the relevant sequences that was an essential element of the invention as claimed. A plurality of the Court considered that to attribute patentability to the invention as claimed would involve an extension of the concept of a manner of manufacture which was not appropriate for judicial determination. 
In the reasoning behind the Australian decision, the Court invoked some similar themes from the U.S. 2013 decision, such as favoring an interpretation of the claims as drawn to information rather than a chemical: 
It follows that in reality the claim in suit is no more expressed in terms of a chemical formula than was the claim in respect of the BRCA1 gene simpliciter which was rejected in the United States. 
The scope of the claims were also cited as concerns: 
Myriad acknowledges that a sample taken from a patient will infringe claim 1 if one or more of the specific mutations and polymorphisms identified in the claim are present, even if the testing is not directed at the BRCA1 gene or the identified mutations and polymorphisms. That is a problem. 
Another international challenge to gene patenting (both product and method claims) remains on deck from Canada, in a case filed by the Children’s Hospital of Eastern Ontario (CHEO) against the University of Utah Research Foundation, Genzyme Genetics and Yale University over the patents covering five genes related to Long QT syndrome, a cardiac disorder. That case is also noteworthy in presenting a patent challenge from a government health provider (CHEO), reflecting the government-centered structure of Canada's healthcare system, where provincial governments assume responsibility in this sector.