Issues Magazine

Intellectual Property – Something Weird’s Going Down in the Patent Office

Issues 96 cover

Issues 96: Intellectual Property

By Luigi Palombi

How can natural DNA, something no person invented, be patented? James Watson, John Sulston, Baruch Blumberg and Joseph Stiglitz think it shouldn’t be.

When Francis Crick, James Watson and Maurice Wilkins were awarded the Nobel Prize in Physiology or Medicine in 1962, the presentation speech described the significance of their breakthrough:

Deoxyribonucleic acid is no staircase in which one can climb; it is a very active biological substance. It has been shown that a number of the steps – most likely three – via another nucleic acid, ribonucleic acid, regulates which amino acids shall be coupled into a protein chain during its synthesis. Thus the order of amino acids in a protein is fundamentally determined by a certain sequence of bases in the nucleic acid. Thus the nucleic acid controls the production of the highly specific proteins, which are the specialized workers of the organism. All the various types of proteins produced take part in a team-work which is subordinated to the needs of the whole organism. Certain characteristics of this team-work, certain specific features in some of the proteins, make the individual unique.

It was on 28 February 1953 that Drs Crick and Watson announced they had cracked the “code”. Their paper, rushed into publication in Nature on 24 April of that year (vol. 171, p. 737) to confirm their breakthrough, was simply entitled “Molecular Structure of Nucleic Acids” and commenced with two understatements: “We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest.”

Almost another 47 years later, the entire human genome was sequenced. On 14 March 2000 US President Bill Clinton and UK Prime Minister Tony Blair issued a joint statement to celebrate the achievement. Describing it as “one of the most significant scientific projects of all time” they went on to make the point that “human DNA sequence and its variations, should be made freely available to scientists everywhere” for the reason that “unencumbered access to this information will promote discoveries that will reduce the burden of disease, improve health around the world, and enhance the quality of life for all humankind.”

Yet, five years later, Kyle Jensen and Fiona Murray published the results of their research in Science (vol. 310 p. 239) entitled “Intellectual Property Landscape of the Human Genome”, showing that “nearly 20% of human genes are explicitly claimed as U.S. IP”.

Today, court battles rage in the US and Australia over the patenting of the genetic mutations to the BRCA1 and BRCA2 human genes linked to familial breast and ovarian cancers. And a failed attempt by four Australian senators to stop the patenting in Australia of naturally occurring biological materials has not deterred Melissa Parke MP, the Labor backbench member for Fremantle, from trying again.

In the 1950s the idea that Crick and Watson would have applied for patents over DNA would have been considered laughable, but recently Watson filed an amicus brief in the court battle over the validity of patents owned by Myriad Genetics that claim, as inventions, the genetic mutations linked to familial breast and ovarian cancers. At stake is the credibility of the entire US patent system.

The Hepatitis C Virus Patent, the “Isolation” Contrivance and Legal Semantics 101

In 1993 I was asked to read a gene patent and provide my client with invalidity advice. It was a routine request, something I had done for many years as a patent litigation partner, except that this time the patent was about a virus: the hepatitis C virus (HCV). And not one strain of that virus, but all six. More than that, the patent contained claims (that is, the formal parts of a patent that define the “invention” and the legal scope of the patent monopoly) to “purified HCV”. The patent, entitled “Non-A Non-B Hepatitis Diagnostics and Vaccines”, was granted by IP Australia with only two minor changes after a perfunctory examination.

Professor Baruch Blumberg, the joint winner of the 1976 Nobel Prize in Physiology or Medicine for his “discoveries concerning new mechanisms for the origin and dissemination of infectious diseases” a few years later testified in his Federal Court of Australia affidavit that the patent’s claims were “very broad”; in fact, so broad he believed “the effect will likely be inhibition on research on HCV”. He was critical because, in his opinion, the patent “represent[ed] a view in scientific thought, i.e., that knowledge of the nucleotide sequence of the virus genome, let alone part of it, tells one all that needs to be known about the functions of the proteins produced by the virus and hence all that needs to be known about the virus”.

Blumberg’s affidavit was one of many I filed in 1994 in the first-ever Australian case to challenge the validity of a gene patent. As the lawyer of record I had identified him as an expert who could help Justice Burchett understand the science, the patent and its implications for medical and scientific research. Australian lawyers for patent owner Chiron Corporation, a US corporation based in San Francisco that was started by some scientists from the University of California, San Francisco, countered by filing the affidavits of Professors Sir Gustav Nossal and John Shine.

The trial ran for nine weeks between June and August 1996. Then it ended. Suddenly, in a worldwide out-of-court settlement negotiated in Chiron’s San Francisco offices, Chiron capitulated to my client’s demands for a worldwide licence to manufacture and sell HCV diagnostic tests. As a result, no judgement was delivered and one of the many questions I was hoping to get an answer to – how could anyone patent a virus? – remained unanswered.

Undeterred, in 1997 I left the law practice I had founded a few years earlier after being sought out by a number of companies that had been threatened by Chiron in its relentless pursuit of its patent rights over the virus. These were not small companies either, with one based in Switzerland and the other in Belgium. The problem for them was, as Baruch Blumberg had predicted, an inability to develop HCV diagnostics and vaccines because of the probability that Chiron would claim any profits as damages for patent infringement.

At the core of Chiron’s patents were the HCV nucleotides and protein claims to those naturally occurring materials in “isolated” or “purified” form. It took another three years for the Technical Appeal Board of the European Patent Office to invalidate over 90% of Chiron’s European HCV patent. Although the Board significantly narrowed its scope so that HCV-antibody testing could be conducted in Europe, the issue over five new patent claims directed to isolated HCV nucleotides and purified proteins submitted by Chiron during the appeal hearing were upheld. As a result, HCV nucleic acid testing remained under Chiron’s legal control, as did any technology subservient to or dependent on those patent claims, such as HCV antivirals.

The decision was political. Only two years earlier the European Parliament passed the European Biotechnology Directive. The Directive is the only piece of legislation anywhere in the world to define a “biotechnological invention” to mean an isolated gene.

The terms “isolation” and “purified” are merely qualifiers used to distinguish between biological materials as they exist in their natural environments and those same materials when removed or separated from those same environments. This is nothing more than legal semantics.

BRCA Patents, the “Isolation” Contrivance and Legal Semantics 101 … Again

It was only a matter of time before the controversy over the patenting of naturally occurring biological materials resurfaced. In the meantime, $3 billion of public money and the combined effort of scientists around the globe had succeeded in mapping the human genome.

Paradoxically, the number of gene patents had exploded. Thousands of patents over every kind of naturally occurring biological material had been granted by patent offices around the world. According to Drs Jansen and Murray, patents over human genes alone covered 4382 of the 23,688 genes in the human genome that were recorded in the National Centre for Biotechnological Information’s database.

In other words, by 2005 a total of 4270 US gene patents were owned by 1156 different patentees of which 63% were private organisations, including the University of California, the only university to come within the top ten of gene patent holders. The other members of that elite group were pharmaceutical and biotechnology companies.

These statistics, however, did not include patents over genetic mutations to those human genes because these are mutations that exist only in the genome of mostly women who are unfortunate enough to carry the genetic triggers of breast and ovarian cancers.

Myriad Genetics, a company spun off by University of Utah researchers whose research into identifying the BRCA genetic mutations was publicly funded, and some venture capitalists, today owns seven US patents and many more patents in other countries that claim, as “inventions”, a set of BRCA genetic mutations linked to familial breast and ovarian cancers. The company holds a 20-year patent monopoly, until its patents expire in 2016, over BRCA testing in the USA.

The cost of a full BRCA1 and BRCA2 test costs about $4000. Apart from the high cost, which has increased over time, Myriad Genetics keeps all of the genetic data generated by the genetic scanning it performs. As a result, women in the US are unable to get a second opinion if the result of the Myriad Genetics BRCA test is positive. There are also many questions over the accuracy or reliability of those tests.

On 12 May 2009, the American Civil Liberties Union funded a patent test case before the US Federal Courts. The suit was brought by 20 plaintiffs, which included the Association for Molecular Pathology, the American College for Medical Genetics, the American Society for Clinical Pathology, the College of American Pathologists and a number of women including Lisbeth Ceriani, who was unable to afford the Myriad Genetics test. Pathologists such as Dr Harry Ostrer and Professor Wendy Chung were also named as plaintiffs. The formal document filed by the plaintiffs outlined the case very simply:

Every person’s body contains human genes, passed down to each individual from his or her parents. These genes determine, in part, the structure and function of every human body. This case challenges the legality and constitutionality of granting patents over this most basic element of every person’s individuality.

Myriad Genetics defended its patent rights. It filed its defence and relied on the “isolation” of the BRCA1 and BRCA2 genetic mutations as the point of distinction that justified the US Patent Office granting it US patents.

In his decision on 30 March 2010, Judge Sweet, a 32-year veteran of the Court, posed the question, “Are isolated human genes and the comparison of their sequences patentable?” He answered it in the negative. The patent claims to the isolated BRCA1 and BRCA2 genetic mutations, and their use in a test that consisted of nothing more than a comparison of genetic information, were, in his opinion “directed to unpatentable subject matter”.

Myriad Genetics immediately appealed Judge Sweet’s decision to the US Court of Appeals for the Federal Circuit. On 29 July 2011, by a two-to-one majority, Judge Sweet’s decision was overturned. According to Judge Lourie, a 21-year veteran of the Court, Judge Sweet got it wrong because “the distinction … turns on a change in the claimed composition’s identity compared with what exists in nature”. Judge Moore concurred but for different reasons. In her opinion, the fact that a BRCA gene in situ is “part of a much larger structure, the chromosome” was a material difference. In dissent, Judge Bryson disagreed. In his opinion:

While the process of extraction is no doubt difficult, and may itself be patentable, the isolated genes are not materially different from the native genes … It may be very difficult to extract the newly found mineral or to find, extract, and propagate the newly discovered plant. But that does not make those naturally occurring items the products of invention.

The US government agreed with Judge Bryson, arguing in an amicus brief to the Court that the US Patent Office had wrongly applied the law.

The plaintiffs then sought to appeal to the US Supreme Court, and although the Court agreed to take the case, instead of hearing oral argument on the issue, on 26 March 2012 it vacated the Court of Appeals’ decision and directed it to rehear the appeal taking into account the guidance provided by the Court’s unanimous decision in Mayo Clinic v. Prometheus handed down only weeks before. In that decision the court invalidated a patent over a diagnostic process on the basis that the patent in issue had claimed a “law of nature”, something that was “not patentable subject matter”.

The US Supreme Court’s decision to vacate the Court of Appeals’ decision was a clear indication that it did not agree with the majority reasoning. And in the lead-up to the second oral hearing before the Court of Appeals, an amicus brief was filed by Dr Watson in which he argued that the various Court decisions missed the point, namely, “the fundamentally unique nature of the human gene”. He said:

Simply put, no other molecule can store the information necessary to create and propagate life the way DNA does. It is a chemical entity, but DNA’s importance flows from its ability to encode and transmit the instructions for creating humans. Life’s instructions ought not be controlled by legal monopolies created at the whim of Congress or the courts.

His words were ignored. On 16 August 2012 the Court of Appeals handed down its second decision. Again the Court was divided two-to-one, holding that the isolated BRCA genetic mutations were patentable.

The case is now heading back to the US Supreme Court.

BRCA Patents, the “Isolation” Contrivance and Politics

Since Genetic Technologies, Myriad Genetics’ exclusive licensee, threatened to sue every laboratory in Australia that performed BRCA testing in July 2008 there have been two Senate inquiries on the issue. A private members Bill to ban gene patenting, sponsored by Senators Heffernan, Coonan, Xenophon and Siewert and supported by MPs Malcolm Turnbull, Rob Oakeshott and Peter Dutton, was also introduced in the Australian Parliament. Unfortunately, the Australian government did not support that Bill. But now, Labor backbencher Melissa Parke is renewing the call for legislative intervention. And an Australian test case brought before the Australian Federal Court by Cancer Voices and Yvonne D’Arcy challenging the Australian Myriad patents is awaiting the decision of Justice Nicholas.

The controversy has raged for 20 years. I never expected it to. It was clear to me in 1993 that the patent system was being misused. And even though the US government has finally recognised this, the Gillard government has, so far, missed the opportunity to get it right.

The matter is now in the hands of the courts. Ironically, Myriad’s BRCA patents expire in 2016.