'Who owns your body?'
A year ago, the US Supreme Court invalidated Myriad Genetics' patents on the BRCA1 and BRCA2 genes, which are at the heart of the company's breast/ovarian cancer risk genetic test. The decision was considered a victory for women — many could not afford to take the test, and those who did had no recourse to a second opinion.
But the Supreme Court decision also had far-reaching, albeit largely unintended, consequences that continue to reverberate in the scientific community and consumer products industry. These consequences go far beyond the issue of genetic testing, according to presenters at an event "Who Owns Your Body? The Ethical, Legal and Economic Implications of Gene Patenting" March 27 at the German Center for Research and Innovation in New York.
Presenters discussed the quixotic history of US patents, the backstory leading up to the Myriad decision, and the potential implications of that decision.
Under the current guidance, patents for all chemicals derived from natural sources — from fats to foods to therapeutics — are being called into question. The ramifications of the ruling are "unclear" at present, the presenters stressed. At the least, it is likely to result in fewer patent applications, as companies increase their use of trade secrets to protect innovations, discouraging transparency and information sharing.[divider]
What's patentable and what's not?
Maneesh Gulati, a partner in the Intellectual Property/Information Technology Group at the law firm McCarter & English LLP in New York, opened the session. He noted that the foundation for the US patent system dates back to Article 1, Section 8 of the US Constitution, commonly known as the "IP (intellectual property) clause." It states that the US Congress may pass laws:
To promote the Progress of Science and useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries.
Subsequently, Congress passed a statute, 35 USC (United States Code) 101, which set the legal foundation for patentable subject matter as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title.
A frequently heard mantra regarding patents is "that which exists in nature — natural principles, products of nature, abstract ideas — are not patentable," Gulati said. "Yet, as noted, neither the constitution nor the statute indicates what is not patentable, only what is patentable."
By giving the alternatives "invents or discovers, "the statute also seems to indicate that the identification of something that already exists in nature might, in fact, be patentable. "Could or should the statute then apply to genes?" he asked. The answer is not as simple as it might seem.
With respect to the life sciences arena, up until a few years ago, the statutory subject matter requirement under 35 U.S.C. 101 was largely a "non-issue," Gulati observed. "But that all changed with the decisions against Myriad, as well as Prometheus Laboratories (regarding the use of certain metabolites to determine drug dose profiles). In my first 10 (of 13) years of practice, I faced less than five rejections dealing with patentable subject matter. But now it's a whole different matter. It's a new beast."[divider]
A capsule case history of 'products of nature'
Dr. Myles Jackson, Research Excellence Professor of NYU Gallatin and Professor of History at NYU, presented a historical look at patent decisions, providing specific examples of ambiguities and inconsistencies about "products of nature" that remain today:
- Ex parte Latimer (1889): The patent office granted a methods patent for extracting pine needles from long-leaf pines, but rejected a patent on the fiber present in the needle because that fiber was deemed a product of nature. However, Dr. Jackson said, "even after that decision, patents were granted for extracted clam juice, for the isolation of a chemical compound in root of a plant that could be used as perfume, and for purified sheep hormones."
- Parke Davis versus Mulford (1911): Justice Billings Learned Hand declared that purified adrenaline for use in a therapeutic product was patentable, despite the fact that adrenaline is a naturally occurring hormone and neurotransmitter. That ruling underlies some of the arguments in favor of Myriad Genetics' patents relating to BRCA1 and 2.
- Funk Brothers Seed versus Kalo Inoculant (1948): Kalo Inoculant's patent for a package of nitrogen-fixing bacteria to be sold to farmers was struck down on the grounds that Kalo had done nothing to change the properties of the bacteria—the company simply created a package for them. That ruling was used in the fight to void Myriad Genetics' BRCA1 and 2 patents.
- Patent Act of 1952: The patent-friendly act stipulates that "anything under the sun made by man" is patentable.
- Merck versus Olin Mathieson Chemical (1958): Merck was permitted to patent a purified vitamin B12 extract, using the adrenaline case as a precedent.
- Joint Communiqué of the US Patent and Trademark Office, European Patent Office and Japanese Patent Office (1988): Agreement that "purified natural products…(are not) products of nature or discoveries because they do not…exist in nature in an isolated form…" Therefore, they are patentable.
Subsequent rulings that a gene is a "chemical compound" and that "purified DNA sequences" could include both naturally occurring and non-naturally occurring sequences laid the groundwork for thousands of US gene patents, many of which are now at risk.[divider]
The BRCA case and its repercussions
Dr. Hans Sauer, Deputy General Counsel for Intellectual Property at the Biotechnology Industry Organization, explained the Myriad decision in detail, as well as its potential implications. He made the point that the Myriad case was not about patenting genes that exist in the body. The patent claims "an isolated DNA that codes for a BRCA-1 polypeptide with a certain amino acid sequence," he said. "Patents have never been permitted to claim things that are in people's bodies. Those are ours alone and they pre-existed in nature. What was being claimed was an isolated preparation of a very long DNA molecule defined by the fact that it encodes for the BRCA protein," Dr. Sauer explained. The lack of clarity on that point in information disseminated to the public "has led to a lot of misperceptions about what these patents actually cover and what they don't."
Nonetheless, after the Supreme Court essentially said that a DNA molecule — even if it's isolated and doesn't claim anything in the body — is not patentable because it's like a "product of nature," Dr. Sauer researched the implications of the decision. "It turns out that many more patents than just Myriad's were affected," he said. Recent estimates suggest at least 8,700 US patents have at least one similar claim on a DNA molecule. "Very few had anything to do with diagnostics, which is what Myriad was about, and only 40 percent even relate to applications in human medicine," he said. "Even before the case was decided, agriculture companies were calling their law firms saying, we don't understand why our patent portfolio could be jeopardized by a case that's only about a single genetic diagnostic company."
The answer, Dr. Sauer said, "is that the legal proposition under which the case advanced through the courts was absolute: Just because you isolate a DNA, it doesn't mean you can get a patent for it." The American Civil Liberties Union (ACLU), which, along with the Public Patent Foundation, brought the case against Myriad, said they did not want it to be just about Myriad; they wanted it to be a test case. "They didn't think any gene, regardless of whether it came from a plant or a bacterium or a human, or whether it's related to breast cancer or laundry detergent manufacturing, should be patentable. And so the Supreme Court was faced with an all-or-nothing decision."
Although the court said not to overinterpret its decision, many other DNA patents could be at risk, Dr. Sauer noted. Follow-on litigation to the Myriad decision included arguments that cell cultures and cell lines should not be patentable, and a request to patent a cloned farm animal was denied because the Patent Office claimed, based on Myriad, that the cloned sheep is a product of nature. Shortly before the GCRI event, the Patent Office came out with a final guidance that stated, according to Dr. Sauer:
Myriad will apply to all chemicals that are derived from natural sources, such as antibiotics, fats, oils, petroleum derivatives, resins, toxins, food products, compositions with grains…metals, metallic compounds, minerals, nucleic acids, proteins and peptides and other substances found or derived from nature … whether the claim is limited to the isolated compound or the recombinant compound or the synthetic compound.
He summed up the current situation this way: "The guidance is unclear and probably internally inconsistent … but there's no question that an expanding universe of subject matter will not even be considered for patenting, that the list is growing and that none of it has anything to do with genetic diagnostic testing."[divider]
An unsettled future
What does the Myriad decision mean for the life sciences sector going forward? According to Dr. Jackson, small genetic sequencing companies "are going to be in big trouble" because many of their patents, which are based on isolated DNA sequences, are likely to be rendered invalid. Companies that do combinatorial chemistry and make new "unnatural" compounds are unlikely to be affected, he said. "But if you're an environmental biotechnology company, for example, and you work on new pathways for degrading compounds using nature as an inspiration, you're going to have a more difficult time."
In lieu of patents, those companies, as well as big pharma, will make more use of trade secrets and licensing agreements, the panelists agreed, though those options will not cover all situations.
Dr. Sauer noted that a colleague who created a synthetic DNA molecule for use in drug- discovery experiments expressed concern after the Myriad decision. Although he searched existing databases to ensure the sequence doesn't exist in nature, he worried what might happen if years from now someone pulled a sea squirt off a coral reef that had a gene with a sequence like the one he created. Would that render his molecule a natural product, jeopardizing his patent?
"I told him I didn't know," Dr. Sauer said. "We hope the law won't develop in such illogical ways, but the truth is, if that happened, he might be in big trouble."
Elsevier Connect Contributor
Marilynn Larkin is an award-winning science writer and editor who develops content for medical, scientific and consumer audiences. She was a contributing editor to The Lancet and its affiliated medical journals for more than 10 years and a regular contributor to the New York Academy of Sciences' publications and Reuters Health's professional newsfeed. She also launched and served as editor for of Caring for the Ages, an official publication of the American Medical Directors Association. Larkin's articles also have appeared in Consumer Reports,Vogue, Woman's Day and many other consumer publications, and she is the author of five consumer health books.