The use of labeled nucleotides as diagnostic tools and agents in genetic screening for disease is at stake in separate lawsuits filed by Enzo Life Sciences against three molecular diagnostics technology companies. Enzo has accused Gen-Probe, Life Technologies, and Roche of infringing on US Patent No. 6,992,180, “Oligo- or Polynucleotides Comprising Phosphate-Moiety Labeled Nucleotides.”
The patent, awarded in January 2006, is based on filings dating back to June 23, 1982 and won’t run out until 2023. “This is a really old technology that they are trying to monetize here in the second decade of the 21st century,” Jonathan D. J. Loeb, Ph.D., a partner in the law firm Dechert, told GEN.
Enzo alleged that its patent was infringed on by no fewer than 14 assays, seven tests, and other products made by the defendant companies. This included a slew of instruments from Roche’s Cobas AmpliPrep, Cobas TaqMan, and Cobas TaqScreen suite of tools like diagnostics for HIV, HCV, HBV, and West Nile virus. The lawsuit covers a number of Life Technologies’ TaqMan assays as well as Gen-Probe’s Aptima line of tests like those for HIV, HCV, HPV, and trichomonas vaginalis.
All three of Enzo’s latest suits were filed January 30 in US District Court for the District of Delaware. Roche, Life Technologies, and Gen-Probe have either promised publicly to fight the lawsuit, without discussing the cases further, or stayed silent. “It’s clear that these parties have been at this for a long time. It must be very important to the defendants since they haven’t settled after all this time, which is pretty unusual,” Dr. Loeb added.
Impact of Case
It’s hard to spell out how much in potential sales is at stake. But it is fair to say that the diagnostics targeted by Enzo are seen by the defendants as significant current or future contributors to their corporate growth.
For example, Roche, which has a roughly one-third market share in the molecular diagnostics sector, said in its annual report that the main sales growth for its Roche Molecular Diagnostics business “came from the HIV and HBV viral load tests and the blood screening business, which grew by 5%.” While Roche’s diagnostics unit finished 2011 with an 8% decline over 2010 to CHF 1.094 billion ($1.213 billion), molecular diagnostics (one of four segments in the diagnostics unit) ended up 4% higher after accounting for constant exchange rates.
Gen-Probe saw a 15%, or $47.2 million, jump in diagnostics sales during 2011, to $353 million. Total product sales grew 8%, or $39.9 million, to $562.6 million; the difference reflects lower blood screening and research product revenues. The latest Aptima product to be approved was the Aptima HPV assay, which won FDA approval on October 31, 2011. Two days later, Gen-Probe president and CEO Carl Hull called Aptima HPV “perhaps the most important incremental driver in our pipeline,” addressing analysts on the quarterly conference call.
When Jonathan Groberg of Macquarie Research Equities asked how long it would take for the Aptima HPV to gain market traction, Hull noted that Qiagen’s rival product had around a 10% share, and added: “Our expectations would be that we can certainly at least do that and better because of the fact that we have both a differentiated assay offering, but more importantly, we’ve got the automated solution.”
Life Technologies’ molecular biology systems division accounted for almost half the company’s total $3.7 billion in revenue last year. The division saw flat revenue in 2011, at $1.7 billion, reflecting lower quantitative PCR royalties and a continued slowdown in sales from academic customers.
Enzo also cited weakness in the academic market in a $0.5 million drop in product revenue down to $9.7 million during the first quarter of its 2012 fiscal year, the three months ending October 31, 2011. During that quarter the company lost $4.5 million on revenues of $25.8 million.
A Decade of Litigation
Dr. Loeb noted that Enzo has spent about a decade battling rival companies over patent rights long before the latest lawsuits. In the most recent of the earlier cases, the US Federal Circuit ruled in favor of Enzo in 2010. It said that two patents previously invalidated by the US District Court, District of Connecticut, and owned by Enzo in a venture with Yale University were valid.
The two patents—Nos. 5,328,824 and 5,449,767—cover a method of using a compound as a diagnostic probe by attaching a nitrogenous base to a chemical moiety through a linkage group. The patents did not claim the linkage group by structure but by function, stating that it did not substantially interfere with hybridization and detection.
Enzo had sued Applera, a predecessor company to Life Technologies, contending that Applera infringed on those two patents, and two others. Applera, and later Life Tech, countered without success that the patents weren’t specific enough in their description of the claimed invention. The District Court had granted summary judgment to Applera for a third patent, No. 5,082,830, after Enzo agreed it could not prove infringement, while holding that a fourth patent, No. 5,476,928, was anticipated from earlier inventions.
The U.S. Supreme Court declined last June to rehear the Federal Circuit decision. That allowed Enzo to proceed with a new patent-infringement suit in the Connecticut district court, with Life Technologies arguing in response that it used a linkage group that “substantially” interferes with hybridization.
The 180 patent uses some of the same language as the patents at issue in the Applera case, by requiring one of two analogs—compounds similar to purine or deazapurine—that do not “substantially interfere” with hybridization.
Enzo’s case against Applera was one of eight cases involving the four patents that have occurred over the past decade. “The practical fact that these parties have been already battling over these technologies for about 10 years, that probably won’t affect the outcome of the new cases, but certainly affects some atmospherics about the war that’s going on,” Dr. Loeb said.
For one thing, he said, parties in years of patent litigation run an increased risk of having their opponent use against them statements made previously in one of the earlier cases. But the Delaware court will have to evaluate the new litigation independent of the older cases.
Additionally, unlike a civil proceeding, where several lawsuits are often consolidated into a single case, the latest Enzo lawsuits will have to remain separate because of a provision in the new Leahy-Smith America Invents Act, the patent-law overhaul enacted in September.
The rule significantly raises the cost for patentees that initiate litigation. That’s no small concern given Enzo’s smaller revenue base compared to the companies it is suing for infringement. “Roche and Life Tech and Gen-Probe haven’t been dissuaded from using this technology, which either means that there aren’t any good alternatives or alternatively that they’re willing to take the risk on these patent cases that they think eventually they’ll work out or they’ll win, or they think the damages won’t be that big,” Dr. Loeb explained.
Whatever their thinking, the companies sued by Enzo can expect a long court fight, since they are battling a plaintiff that has 11 years left on the 180 patent. Hopefully, it will take far less time than that for the Delaware district court to weigh in or, even better, for the companies involved to settle their dispute.