This month, Myriad announced that it plans to launch a hereditary cancer panel based on next-generation sequencing by the end of the year and that it would phase out its Sanger-based BRACAnalysis test by 2015, causing some experts to speculate how Myriad's entry into next-gen sequencing-based diagnostics could impact the burgeoning cancer panel market.
Currently, a number of companies have launched next-gen cancer panels or have plans to develop them. The major next-gen sequencing vendors Illumina and Life Technologies already offer research-use-only cancer panels, which some laboratories are adopting for clinical use.
While Myriad will have less expertise in next-generation sequencing, the company has a strong presence in cancer predisposition testing. Due to its patent portfolio, it has a monopoly on testing for mutations in BRCA1 and BRCA2 genes, which are associated with an increased risk for breast and ovarian cancer.
Because Myriad holds patents around those genes, firms such as Ambry Genetics do not include BRCA1 and BRCA2 genes in their clinical hereditary cancer panels. GeneDx includes the genes in its clinical exome test, but does not Sanger-confirm mutations.
Additionally, while Illumina includes the BRCA1 and 2 genes in its RUO TruSight hereditary cancer panel, the firm instructs customers on its website that they are responsible for ensuring they have the necessary licenses for all proprietary content. By contrast, Life Technologies includes no such disclosure on its AmpliSeq website, where it sells an RUO BRCA1/2 panel. Illumina and Life Tech declined to comment for this article.
Recently, Myriad claimed that it holds intellectual property around a number of important cancer-related genes, many of which are included in competitors' offerings, sparking questions as to whether it would enforce those patents when it launches its own NGS cancer panel.
"Does Myriad really want to sue in a case that might once again go all the way to the [US Court of Appeal for the Federal Circuit] and possibly the Supreme Court?" asked Robert Cook-Deegan, director of Duke University's Center for Genome Ethics, Law & Policy, via email.
Method of use
During a conference call discussing its first-quarter 2013 financial results, Myriad CEO Peter Meldrum said that the company has "strong method of use patent protection around many of the key genes that may be important in any pan cancer panel."
Many of these genes are on NGS panels currently being offered, and the myRisk cancer panel that Myriad is developing will include eight genes for which Myriad holds intellectual property: BRCA1, BRCA2, BART, RAD51C, PALB2, PTEN, MYH, and P16.
Many of these method of use patents are not the ones currently being examined by the Supreme Court in the Association for Molecular Pathology v. Myriad Genetics lawsuit. However, several of Myriad's method patents around BRCA1 and 2 that described "comparing" and "analyzing" gene sequences have already been invalidated by lower courts (PGx Reporter 8/3/2011).
In the suit, the plaintiffs are challenging nine of Myriad's patent claims for the BRCA1 and BRCA2 genes, which include claims covering stretches of isolated DNA as well as cDNA, as reported by sister publication Pharmacogenomics Reporter (PGx Reporter 4/17/2013).
The plaintiffs argue that the patents on isolated DNA sequences are invalid because they are identical to what is found inside a person's body.
The method patents differ from the patents on isolated DNA and cDNA because they concern how those sequences are used.
During its recent investor day conference, Meldrum assured investors that the company's "method of use claims are very strong and that will continue to give Myriad a very strong intellectual property competitive advantage going forward with myRisk" (CSN 5/15/2013).
However, some question the breadth of these methods claims, especially in light of the previously invalidated patents. According to Credit Suisse analyst Vamil Divan, there is "controversy around the strength of [Myriad's] method of use patents."
Cook-Deegan said that not all of Myriad's method of use patents apply to diagnostics. Others, like its PALB2 patent is specific to pancreatic cancer, he said.
Additionally, the firm's method patents may not be applicable to next-generation sequencing tests and may cover only the PCR-based methods similar to what Myriad uses in its BRACAnalysis tests, said Cook-Deegan.
If the Supreme Court rules against Myriad and additional laboratories start including BRCA1 and 2 on their cancer panels, Myriad's "IP position will suddenly be very hard to enforce," Cook-Deegan said.
Sherri Bale, managing director at GeneDx, also did not think that Myriad's claims around method of use patents on cancer genes would stop laboratories from developing panels that include those genes. "Generally, I think the whole idea of patenting in this industry is so questionable about what's going to stand, that I think people will go ahead with [their panels]," she said.
As such, most say that Myriad's continued dominance in cancer predisposition testing rests largely on the outcome of the Supreme Court trial.
If Myriad's patents are upheld, competitors could face lawsuits for launching panels that include the BRCA genes. But, if the suit is overturned, laboratories developing such tests will be able to include the genes, and Myriad's entry into the NGS space may have less of an impact.
The "competition comes down to BRCA," said Divan. "If only Myriad can offer a truly comprehensive test that includes BRCA1 and 2, and with their analysis expertise, they have a real competitive advantage."
On the other hand, if Myriad loses its case, "there are a lot of people offering [NGS] panels that can easily add BRCA1 and 2 to it," he added.
A number of companies, including GeneDx, have said they are set to launch tests for BRCA1 and 2 mutations as soon as the court makes its ruling (PGx 4/17/2013).
If Myriad loses its monopoly on BRCA testing, the firm will have to compete with other providers on cost, quality, and efficiency.
Currently, Myriad's BRACAnalysis tests cost $3,000 to $4,000. However, tests that analyze many more genes are being offered at comparable prices.
According to Ambry's website, using the relevant CPT codes, it charges $4,120 for BreastNext, its hereditary cancer panel that analyzes 14 genes, not including BRCA1 and BRCA2. Meantime, GeneDx charges $5,000 for its XomeDx test, which analyzes the entire exome of an affected individual. The BRCA1 and 2 genes are included in the XomeDx test, but mutations are not Sanger-confirmed.
Myriad may have an advantage in its clinical database that it has built up over years of testing and expertise in interpreting BRCA mutations, said Divan, but "that's more of a short-term advantage," particularly if the Supreme Court rules against the firm and other companies are able to build up their own databases of BRCA mutations.
And, "efforts are being made to build public domain information sources to supplant [Myriad's] database," Cook-Deegan added.
Once competitors enter the market with BRCA1 and 2 tests or panels that include the BRCA genes, Myriad's "only asset will be a million-test database, the samples they have accumulated and use to validate a multi-gene test, and the payment agreements they've gotten with payors," Cook-Deegan said.
He added that payors are price sensitive, so if companies or even academic institutions like the Mayo Clinic or Baylor College of Medicine begin offering lower-cost versions, payors may switch to cover those tests. "I'm willing to bet this market is about to get disrupted over the next few months," he said.