Supreme Court: Prometheus Decision a Harbinger for Myriad?

Posted under Blog, Companies, Diagnostics, Funding, gene therapy, IP, Legal, Medical Devices, Medical Supply, patents, Pharmaceuticals, Regulatory, Startups, Strategy, United States Supreme Court, Universities, Videos by Ben Comer

In judging the Prometheus patents invalid, the Supreme Court may have shown its hand on the upcoming Myriad Genetics case.

In a unanimous decision on Tuesday, the Supreme Court stripped two Prometheus patents on the grounds that the company didn’t go far enough beyond merely identifying a natural law. Natural laws – a product of the natural phenomenon doctrine in patent law, are the province of everyone in the US, ever since Justice Rehnquist wrote in 1981 that “laws of nature, natural phenomena, and abstract ideas” aren’t patentable.

But to what extent must a biopharma organization show an application of a natural law, to support a claim? In Mayo Collaborative Services v. Prometheus Laboratories, the latter held two patents describing a method for optimal dosing of thiopurine for autoimmune disorders. To wit: if metabolite levels are too high with patients using thiopurine drugs, toxicities are likely to occur; if they’re too low, the drugs lose efficacy in the patient. Prometheus markets a blood test to measure metabolite levels, and the Mayo Clinic, acknowledging the relationship to thiopurine dosage and efficacy, created it’s own blood test to be used by physicians. Prometheus (acquired by Nestle last May) sued, claiming the Mayo Clinic violated its patents, and despite winning a Federal Circuit decision, the Supreme Court begged to differ.

With the Myriad Genetics case on the Supreme Court’s horizon, some attorneys following both cases are predicting another reversal. In the Prometheus decision, the court directly cites an amicus brief from two organizations – the American College of Medical Genetics, and the Association for Molecular Pathology – in defense of its judgment; both organizations are also named plaintiffs in the Myriad case. The amicus brief quoted in the Prometheus decision argues that if “claims to exclusive rights over the body’s natural responses to illness and medical treatment are permitted to stand, the result will be a vast thicket of exclusive rights over the use of critical scientific data that must remain widely available if physicians are to provide sound medical care.”

This is precisely the argument being made against Myriad, which holds patents on two genes known as BRCA1 and BRCA2; mutations in those two genes are associated with increased risk of breast and ovarian cancer, and Myriad sequences the genes to reveal the mutations. In light of the Prometheus decision, “there is a good chance the Supreme Court will remand the pending Myriad Genetics case to the Federal Circuit, to have it reconsider its opinion,” says Craig Smith, a partner at Lando & Anastasi. The Federal Circuit court ruling on Myriad upheld patent claims on isolated DNA, defined by patent law as composition of matter claims, but the diagnostic claims made by Myriad – first debunked by United States District Court Judge Robert Sweet – were similarly refuted by the Federal Circuit. Judge Sweet also stripped the BRCA1 and BRCA2 gene patents, but the Federal Circuit court reinstated those patents.

Many companies have gene patents; Myriad is hardly the first to receive composition of matter patents on genes. However, the argument that patents stifle, or erect barriers to medical research, seems to be gaining traction with the Supreme Court. “I’m not buying the argument that the court threw in there as a policy palliative…it seems to me that the court is saying the [Prometheus] claims go to far, and any benefits from patent protection are outweighed by the chilling effect on future innovation,” via medical research, says James Mullen, partner at Morrison & Foerster. How strongly this argument is made will have a least some bearing on the Myriad outcome, although gene patents are more or less entrenched as precedent.

What does this mean for industry? Unfortunately, the Promethius case offers little in the form of new guidance. If a claim is so broad as to state a law of nature, with the added suggestion that it be applied, it won’t be considered patentable, but “everyone knew that ahead of time,” says Mullen. “I think the decision creates more uncertainty,” because “the Court didn’t give any signposts as to what level of post-solution activity is necessary to go beyond the order to ‘go out and apply this law,’ which isn’t a patentable claim…there was no detail as to what application – by doing a, b, or c – by opening the mold for your rubber plant, at a particular temperature point, like the Court did with Diamond v Diehr.”

D’vorah Graeser, CEO at Graeser Associates International, says the Prometheus decision, and the upcoming Myriad case, may cast a “pall over the entire diagnostic industry.” Without specific guidance, “Where do you draw the line?” wonders Graeser. “Is it having an antibody involved, or some kind of machinery? From the Prometheus decision, it’s impossible to tell.”

U.K. green lights study of pioneering gene therapy against cystic fibrosis

Posted under Blog, Clinical Trials, Companies, cystic fibrosis, Diagnostics, drug delivery systems, Funding, gene therapy, genetic mutation, Medical Devices, Medical Supply, Pharmaceuticals, Startups, Universities, Videos by Ryan McBride

Researchers in the U.K. plan to launch a mid-stage clinical trial this month for an inhaled gene therapy to combat cystic fibrosis (CF). The U.K.'s National Institute for Health Research and Medical Research Council have ponied up £3.1 million ($4.9 million) in funding to get the trial off the ground.

U.K. Cystic Fibrosis Gene Therapy Consortium, a nonprofit research group, will coordinate the 130-patient trial, which the consortium called the largest of its kind and will include patients aged 12 and up. Patients in the double-blind, placebo-controlled study will get a dose of the gene therapy or a placebo once per month over the course of a year, with results expected in spring 2014, according to the group's release.

Cystic fibrosis is a genetic disease that causes a buildup of thick, sticky mucus in the lungs and leads to respiratory infections and other debilitating symptoms. In the U.K. the only available treatments address only the symptoms of the chronic condition, and CF patients have an average life expectancy of 41 years, the PharmaTimes reports. The consortium has been working for more than a decade on their gene therapy, which is inhaled into the lungs to deliver molecules of DNA into cells to replace the defective gene that causes CF.

The Medical Research Council has also come up with £1.2 million ($1.9 million) to fund research of a modified virus as a vehicle to provide improved delivery of the gene therapy.

CF patients are forced to take a battery of treatments to control the symptoms of their disease, yet in recent years, companies such as Vertex Pharmaceuticals ($VRTX) have advanced treatments that address the root genetic cause of the disease rather than just the symptoms. The FDA in January stamped an approval on Vertex's Kalydeco, a targeted drug for about 4% of CF patients in the U.S. who have the G551D mutation. And the drug developer is now working on other targeted approaches to address the root cause of the disease.

- get the consortium's release
- read the PharmaTimes article

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Highlights from the Leerink Swann Healthcare Conference

Posted under Blog, CDER, Companies, companion diagnostics, conference, Diagnostics, DNA, Events, FDA, Funding, gene therapy, genetics, Janet Woodcock, leadership, Leerink Swann, Medical Devices, Medical Supply, Next Generation Sequencing, Pharmaceuticals, Startups, Strategy, Technology, Universities, Videos by Ben Comer

Over a hundred public companies, dozens of clinicians, and several regulators participated in investment firm Leerink Swann’s 2012 Healthcare Conference in mid-February. Press was barred from the event, but John Sullivan, Leerink’s director of research, gives PharmExec a few of the take-aways.

Everyone knows that Dr. Janet Woodcock, CDER’s director, tends to stress the importance of safety as FDA’s top mission when speaking to a public audience. During a keynote address at the Leerink Swann Healthcare Conference in February, she also spoke about the importance of transparency and communication at FDA, specifically with respect to smaller biotech companies.

John Sullivan, Leerink Swann’s director of research, was intrigued by Woodcock’s comments. With an increase in the number of smaller companies, including small biotechs, appearing before the FDA as drug sponsors, Woodcock acknowledged that a different method of interaction, with different protocols, is necessary. “When your customers are big drug companies, they’re more likely to know the language…you have career regulatory officers on board internally, and a lot more shots on goal,” says Sullivan. “You can send them away with a previously unclear piece of guidance that hasn’t been clarified, and they’ll go do more work, confident in the knowledge that they’ll be back in front of the agency with that candidate or another one. They have a certain way of interacting that’s long-term in nature.”

With smaller companies, like emerging biotechs, however, the drug candidate up for review may be a company’s only product, or one of a very few. “There’s a heightened level of urgency that I think the FDA is now recognizing,” says Sullivan. “It sounds like they are taking specific steps to make themselves more available to smaller drug sponsors, to give them more guidance.” Hopefully, this will help to minimize the risk of a company going out and conducting new trials, only to reappear two or three years later to find out that the trial wasn’t what the FDA wanted, in terms of design, says Sullivan. “I took [Woodcock’s comments] as a positive at the margin. That doesn’t mean that this class of emerging biotechs will get more approvals out of FDA, but hopefully they’ll get the right answers, perhaps a bit sooner and for a bit less money, than what they might have anticipated.”

Woodcock has also been an outspoken proponent of drug and diagnostic combinations, and in addition to panels on new prostate cancer treatments, duel eligible and healthcare exchanges, biosimilars, rheumatology and other topics, Leerink also convened a panel on clinical DNA sequencing. The panel focused on the migration of sequencing toward the clinic. The panel consensus, according to Sullivan, was that DNA sequencing would inevitably come to the clinic, but not before two things happen: “The price has to come down, and the utility of the DNA sequence information, to the clinician and his or her patient, has to go up.” Per Sullivan, more links between genetic presentation and predisposition for disease, or response to therapy, need to be made. The platforms by which cancer diagnosis and treatment are used today are “relatively low-density…they can do maybe ten genes or 50 genes,” says Sullivan. With full genome sequencing, researchers can do tens of thousands of genes at once, but “most clinicians don’t need, nor do they know what to do with that volume of information.” Panelists said that as clinicians learn more about genetic information, and the price of a full scan comes down, patients will start to be scanned more often.

“I think there was broad agreement that DNA sequencing, especially single-molecule sequencing – where you don’t have the risk of mistakes as you amplify the amount of genetic material for analysis – really holds the promise of being more accurate than other methods of interrogating DNA and RNA, so it’s attractive from the standpoint of physicians, who want to make sure they’re giving the right answer. DNA sequencing, especially single molecule sequencing, increases those odds,” says Sullivan.

On the issue of price, Illumina and Life Technologies announced in the respective launches of two platforms that can sequence an entire genome for $1,000, in one day’s time. Sullivan called Illumina, which is currently subject to a hostile takeover attempt by Roche (the bid is currently $5.7 billion), a “leader in research-based DNA sequencing today.” Ion Torrent, acquired in 2010 by Life Technologies (which was itself formed through the merger of Invitrogen Corp and Applied Biosystems, in 2008) released a mock-up photograph of a clinical DNA sequencing instrument small enough to fit in the hand of a physician. While still a ways off, the photo suggests DNA sequencing in the clinic will require a set of tools that differs from what’s currently used in the lab, by researchers, says Sullivan. “Clinicians and clinical lab staffers have very different needs than research lab PhDs,” he says. “As far as the drug industry is concerned, they’ll continue to get good ideas for new products from the genetic research studies that are going on in a million academic research labs all over the world, and they will increasingly look to pair their drugs – whether genetically derived or not – with diagnostics.”

Gene therapy study offers proof of potential breakthrough on hemophilia

Posted under Blog, Companies, Diagnostics, Funding, gene therapy, hemophilia, Medical Devices, Medical Supply, Pharmaceuticals, Startups, Universities, Videos by John Carroll

A transatlantic team of investigators has presented some promising--though very early stage--breakthrough data on a new gene therapy for hemophilia B. The investigators say that their gene therapy program came close to curing four of 6 patients, spurring the body to produce enough clotting factor to eliminate the need for regular protein injections. And the other two were helped by the treatment, with a reduced need for injections.

One in every 30,000 people carries a genetic defect that prevents them from producing a protein, Factor IX, which the body needs to create a natural blood clotter. Building on 25 years of gene therapy work, the team from University College London and St. Jude Children's Research Hospital adapted a benign virus to essentially infect liver cells with the right genetic material. And a 20-minute infusion pushed levels of Factor IX to a range of two percent to 12% of normal. The high end of that range is enough to eliminate most of the lethal threats posed by hemophilia.

"They would be able to go about their normal daily lives without any problems," Dr. Amit Nathwani from University College London told the BBC. "The only time that they would have a problem is if they were involved in a road traffic accident or had a big fall from a building site. In the absence of severe major trauma these individuals would not know that they have haemophilia."

That's good, but the researchers are targeting a 20% hike in Factor IX levels and they'll be tweaking their gene therapy approach to try and get there. They'll also be looking to avoid a spike in liver enzymes seen in two patients, a classic warning signal in drug development.

"The idea of treating hemophilia with gene therapy has been around for 25 years, but the problem was how to do it right," Ronald G. Crystal, chairman of the department of genetic medicine at Weill Cornell Medical College, tells The Wall Street Journal. "This is an important breakthrough because it is the first success in one of the plasma deficiency disorders and shows gene therapy is feasible."

- read the story from the BBC
- get The Wall Street Journal's article

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