Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News
Advice focuses on ensuring transformative steps are included in claims.
The U.S. Supreme Court angered some with its decision to overturn Prometheus’ patents on a drug-dosage calibration method by saying the measurement was too close to a natural phenomenon. And today the Supreme Court “G-V-Red” Myriad—as in granted certiorari to take the case, then vacated the 2010 decision by the Court of Appeals for the Federal Circuit, and remanded the case to the federal circuit for re-review in accordance with the high court’s decision in Prometheus v. Mayo.
Those who disagree with the outcome of Prometheus v. Mayo fear the decision will hold back personalized medicine by stoking more litigation and confusing molecular diagnostic companies about what they can patent. Others say that the ruling won’t be a major setback for the field and gives companies an idea about how to write claims.
“A lot of people are being Chicken Little and saying ‘The sky is falling,’ but I don’t think it will be that big of a negative impact on personalized medicine,” Lisa A. Haile, Ph.D., a partner at DLA Piper U.S. and co-chair of the firm’s global life science sector group, told GEN. “The court is giving us some very good guidance as to what claims probably should look like if they want to be considered valid.”
Which side is right will become evident soon as the courts decide on the legal wrangle over seven Myriad Genetics patents related to BRCA1 and BRCA2 genes and the company’s method for analyzing those genes for mutations associated with breast cancer.
In Myriad’s case, known as Association of Molecular Pathology et al. v. US Patent and Trademark Office (AMP v. USPTO), the U.S. District Court’s Southern District of New York previously sided with AMP. The Federal Circuit overturned most of that decision, finding Myriad’s gene claims and its methods of screening for cancer compounds patentable but not the company’s claims for mutation analysis.
In its March 20 Prometheus v. Mayo decision, the Supreme Court invalidated two Prometheus Laboratories patents covering its dosage calibration methods for thiopurine drugs for gastrointestinal and nongastrointestinal autoimmune diseases. The high court overturned a Federal Circuit decision upholding the patents, which covered methods designed to take into account the context of a treatment regimen based on the individual patient’s metabolism.
With regard to Myriad, “the diagnostic claims, I think, are potentially still invalid based on Prometheus,” Dr. Haile predicted. “But I would say the gene patent claims will come out of the Federal Circuit again as patent-eligible subject matter. The Federal Circuit will ask, ‘Are these sequences just a law of nature, and what have you done with them?’
“I think the Federal Circuit is going to stick with its original decision,” Dr. Haile remarked. “They’re going to say, ‘You’re doing more than just observing the DNA: You have cut it out from its naturally occurring environment now, and you’ve isolated it. I think they’re going to say that that’s enough for the transformation step.”
Prometheus’ claims may have survived, she said, if they included additional steps: “Maybe even to the level of saying how you determine the level of the drug: Did you do a blood test? Whatever it is, there just seems to be a need for some more active steps so you could see there was something beyond just making an observation.”
Prometheus ran into legal trouble by failing to persuade judges that its process steps added enough to the laws of nature to make its claims patentable subject matter, Gerald J. Flattmann Jr., a partner in the intellectual property practice of Paul Hastings, added.
While Prometheus used a dosage-determination step that the Supreme Court deemed too close to an unpatentable law of nature, Myriad’s rejected mutation analysis patent merely required comparison of a mutation sequence with a control sequence, with no additional step such as assaying or isolating the gene and determining the sequence, Daniel J. Nevrivy, Ph.D., founder of the Nevrivy Patent Law Group, told GEN. “There’s no transformative step in the way that there is a transformative step in Prometheus’ claims of determining or administering. In Myriad, the claim is purely mental.”
And while the Federal Circuit suggested that some isolation step in that claim might have saved that claim, “if you look at the decision in Mayo, by the Court’s reasoning, it’s highly doubtful or it’s very questionable whether such a claim would be patent eligible,” Dr. Nevrivy added. In Myriad, a three-judge panel of the Federal Circuit concluded that the steps involved in growing cells containing a BRCA1 or BRCA2 gene and in manipulating the growth of those cells in the presence or absence of a cancer therapeutic did not constitute just observation but involved transformation of the cell culture.
The Myriad case involves patents with both composition and method claims, compared with just the method claims in Prometheus. “How those composition claims in Myriad would be analyzed would not necessarily be in the same way as the claims in the Prometheus v. Mayo case,” Dr. Nevrivy added.
Flattmann cited Myriad’s argument that its claimed isolated DNA fragments are not products of nature and hence do not implicate the general prohibition against patenting products of nature, abstract ideas, and laws of nature.
It’s fair to say whoever loses in Federal Circuit will push the Myriad case back to the Supreme Court “given the importance of the case and the attention of a number of interested parties,” Paul Rivard, a shareholder with Banner & Witcoff, noted. “I think it’s likely at some point when these issues get back before the Supreme Court that the Supreme Court is going to inject the same concerns they had in Prometheus. In the case of isolated DNA, for example, the Supreme Court may say, ‘these are routine steps for isolating the DNA fragments that have been practiced; there’s nothing special or out-of-the-ordinary about the steps that take this naturally occurring material to a man-made material and that we’re not going to give weight to that. That’s possibly how the Supreme Court would look at that issue based on some of their statements in Prometheus.”
Impact on Personalized Med
“The Prometheus case erases the bright line that the Federal Circuit gave us with the transformation of the method of treatment and sort of leaves us to figure out where the next line can be drawn,” said Courtenay C. Brinckerhoff, a partner with Foley & Lardner. “If you have claims that are optimizing the dosage of known drugs, maybe you’re going to have to take a look at those, whereas if you have claims that relate to a new drug or a new metabolite of that drug, maybe your claims are not really impacted.”
Flattmann noted, “The decision is not terribly surprising given the odd and idiosyncratic way the claims at issue were written. If applied narrowly as limited to its facts by the District Courts and Federal Circuit, the holding ought not have any major negative effect on patentees and, in particular, on innovation in the field of personalized medicine.”
One potential danger, he added, is that courts may misapply the Mayo decision as broadly requiring invalidation of any claim that recites a law of nature among its steps: “Such misapplication would have a profound negative impact on innovation in the field of personalized medicine and beyond since, of course, all invention is on some level based on the practical application of natural discoveries.”
Dr. Haile advises companies to examine their IP and consider pursuing reissues of patents, which if rewritten to narrow claims, such as adding steps, can be done during the life of existing patents; patents can only be broadened within two years of issue.
Predicting more challenges for industry from Prometheus is Hans Sauer, Ph.D., deputy general counsel, intellectual property at the Biotechnology Industry Organization (BIO). “We have member companies who are incredulous that the patent claims that are built around these discoveries would now be subjected to this new analysis that the Supreme Court promulgated,” Dr. Sauer said.
“You take out the very principle that a claim is built around—say, a new biological discovery of why your drug works—and you eliminate that from consideration. You look at the rest of the patent claim, and you ask, is the rest of this inventive or not? Of course it’s not. Your invention was just eliminated from the claim, so of course the rest looks unimpressive and old.”
Dr. Sauer said it was hard to say how the Prometheus opinion will play out, let alone its likely effect on the Myriad case. “Because this opinion is going to be very, very difficult to implement in practice, maybe its impact is going to be limited for that reason. There’s not a lot of guidance. There’s only more uncertainty in this opinion for patent law.
The Supreme Court decision won’t derail personalized medicine, Dr. Sauer said, but will make it harder for companies to find additional investor capital. For companies seeking capital, he said, the options will likely include taking less money, accepting more strings, or switching to safer, less innovative development programs.
That doesn’t bode well, for example, for companies seeking to transform failed drugs into successful, more targeted medicines through biomarker screening. “The scientist who discovers why the drug only worked in 10% of all patients, that scientist didn’t discover a law of nature. What that is, is the difference between a failed drug and a drug that reaches the marketplace and benefits real people,” Dr. Sauer said.
In Prometheus, the Supreme Court answered one question but created another legal riddle concerning method-claim patentability that maybe Myriad can resolve. According to the court: “A patent must do more than simply state the law of nature while adding the words ‘apply it.’ It must limit its reach to a particular, inventive application of the law.” But just what is a particular inventive application? The court missed an opportunity to answer that question and in so doing ensured another lengthy legal wrangle for personalized medicine.
Alex Philippidis is senior news editor at Genetic Engineering & Biotechnology News.